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Warning:
This document is being maintained for historical purposes, but is now out of date. To view current guidelines please visit:
- STD Treatment Guidelines at http://www.cdc.gov/STD/treatment
1998 Guidelines for Treatment of Sexually Transmitted Disease
Date: 01/23/98
Source: 47(RR-1);1-118
SUGGESTED CITATION: Centers for Disease Control and Prevention. 1998 Guidelines for Treatment of Sexually Transmitted Diseases. MMWR 1998;47(No. RR-1): {inclusive page numbers}.
The material in this report was prepared for publication by: National Center for HIV, STD and TB Prevention, Division of Sexually Transmitted Diseases Prevention
DISEASES CHARACTERIZED BY URETHRITIS AND CERVICITIS
Management of Male Patients Who Have Urethritis
Urethritis, or inflammation of the urethra, is caused by an infection characterized by the discharge of mucopurulent or purulent material and by burning during urination. Asymptomatic infections are common. The only bacterial pathogens of proven clinical importance in men who have urethritis are N. gonorrhoeae and C. trachomatis. Testing to determine the specific disease is recommended because both of these infections are reportable to state health departments, and a specific diagnosis may improve compliance and partner notification. If diagnostic tools (e.g., a Gram stain and microscope) are unavailable, patients should be treated for both infections. The extra expense of treating a person who has nongonococcal urethritis (NGU) for both infections also should encourage the health-care provider to make a specific diagnosis. New nucleic acid amplification tests enable detection of N. gonorrhoeae and C. trachomatis on first-void urine; in some settings, these tests are more sensitive than traditional culture techniques.
Etiology
NGU is diagnosed if Gram-negative intracellular organisms cannot be identified on Gram stains. C. trachomatis is the most frequent cause (i.e., in 23%-55% of cases); however, the prevalence differs by age group, with lower prevalence among older men. The proportion of NGU cases caused by chlamydia has been declining gradually. Complications of NGU among men infected with C. trachomatis include epididymitis and Reiter's syndrome. Documentation of chlamydia infection is important because partner referral for evaluation and treatment would be indicated.
The etiology of most cases of nonchlamydial NGU is unknown. Ureaplasma urealyticum and possibly Mycoplasma genitalium are implicated in as many as one third of cases. Specific diagnostic tests for these organisms are not indicated.
Trichomonas vaginalis and HSV sometimes cause NGU. Diagnostic and treatment procedures for these organisms are reserved for situations in which NGU is nonresponsive to therapy.
Confirmed Urethritis
Clinicians should document that urethritis is present. Urethritis can be documented by the presence of any of the following signs:
Mucopurulent or purulent discharge.
Gram stain of urethral secretions demonstrating greater than or equal to 5 WBCs per oil immersion field. The Gram stain is the preferred rapid diagnostic test for evaluating urethritis. It is highly sensitive and specific for documenting both urethritis and the presence or absence of gonococcal infection. Gonococcal infection is established by documenting the presence of WBCs containing intracellular Gram-negative diplococci.
Positive leukocyte esterase test on first-void urine, or microscopic examination of first-void urine demonstrating greater than or equal to 10 WBCs per high power field.
If none of these criteria is present, then treatment should be deferred, and the patient should be tested for N. gonorrhoeae and C. trachomatis and followed closely in the event of a positive test result. If the results demonstrate infection with either N. gonorrhoeae or C. trachomatis, the appropriate treatment should be given and sex partners referred for evaluation and treatment.
Empiric treatment of symptoms without documentation of urethritis is recommended only for patients at high risk for infection who are unlikely to return for a follow-up evaluation (e.g., adolescents who have multiple partners). Such patients should be treated for gonorrhea and chlamydia. Partners of patients treated empirically should be referred for evaluation and treatment.
Management of Patients Who Have Nongonococcal Urethritis
Diagnosis
All patients who have urethritis should be evaluated for the presence of gonococcal and chlamydial infection. Testing for chlamydia is strongly recommended because of the increased utility and availability of highly sensitive and specific testing methods and because a specific diagnosis might improve compliance and partner notification.
Treatment
Treatment should be initiated as soon as possible after diagnosis. Single-dose regimens have the important advantage of improved compliance and of directly observed therapy. If multiple-dose regimens are used, the medication should be provided in the clinic or health-care provider's office. Treatment with the recommended regimen can result in alleviation of symptoms and microbiologic cure of infection.
Recommended Regimens
Azithromycin 1 g orally in a single dose,
OR
Doxycycline 100 mg orally twice a day for 7 days.
Alternative Regimens
Erythromycin base 500 mg orally four times a day for 7 days
OR
Erythromycin ethylsuccinate 800 mg orally four times a day for 7 days,
OR
Ofloxacin 300 mg twice a day for 7 days.
If only erythromycin can be used and a patient cannot tolerate high-dose erythromycin schedules, one of the following regimens can be used:
Erythromycin base 250 mg orally four times a day for 14 days,
OR
Erythromycin ethylsuccinate 400 mg orally four times a day for 14 days.
Follow-Up for Patients Who Have Urethritis
Patients should be instructed to return for evaluation if symptoms persist or recur after completion of therapy. Symptoms alone, without documentation of signs or laboratory evidence of urethral inflammation, are not a sufficient basis for re-treatment. Patients should be instructed to abstain from sexual intercourse until therapy is completed.
Partner Referral
Patients should refer for evaluation and treatment all sex partners within the preceding 60 days. A specific diagnosis may facilitate partner referral; therefore, testing for gonorrhea and chlamydia is encouraged.
Recurrent and Persistent Urethritis
Objective signs of urethritis should be present before initiation of antimicrobial therapy. Effective regimens have not been identified for treating patients who have persistent symptoms or frequent recurrences after treatment. Patients who have persistent or recurrent urethritis should be re-treated with the initial regimen if they did not comply with the treatment regimen or if they were reexposed to an untreated sex partner. Otherwise, a wet mount examination and culture of an intraurethral swab specimen for T. vaginalis should be performed. Urologic examinations usually do not reveal a specific etiology. If the patient was compliant with the initial regimen and reexposure can be excluded, the following regimen is recommended:
Recommended Treatment for Recurrent/Persistent Urethritis
Metronidazole 2 g orally in a single dose,
PLUS
Erythromycin base 500 mg orally four times a day for 7 days,
OR
Erythromycin ethylsuccinate 800 mg orally four times a day for 7 days.
Special Considerations
HIV Infection
Gonococcal urethritis, chlamydial urethritis, and nongoncoccal, nonchlamydial urethritis may facilitate HIV transmission. Patients who have NGU and also are infected with HIV should receive the same treatment regimen as those who are HIV-negative.
Management of Patients Who Have Mucopurulent Cervicitis (MPC)
MPC is characterized by a purulent or mucopurulent endocervical exudate visible in the endocervical canal or in an endocervical swab specimen. Some experts also make the diagnosis on the basis of easily induced cervical bleeding. Although some experts consider an increased number of polymorphonuclear leukocytes on endocervical Gram stain as being useful in the diagnosis of MPC, this criterion has not been standardized, has a low positive-predictive value (PPV), and is not available in some settings. MPC often is asymptomatic, but some women have an abnormal vaginal discharge and vaginal bleeding (e.g., after sexual intercourse). MPC can be caused by C. trachomatis or N. gonorrhoeae; however, in most cases neither organism can be isolated. MPC can persist despite repeated courses of antimicrobial therapy. Because relapse or reinfection with C. trachomatis or N. gonorrhoeae usually does not apply to persistent cases of MPC, other non-microbiologic determinants (e.g., inflammation in an ectropion) could be involved.
Patients who have MPC should be tested for C. trachomatis and for N. gonorrhoeae by using the most sensitive and specific test for the population served. However, MPC is not a sensitive predictor of infection with these organisms, because most women who have C. trachomatis or N. gonorrhoeae do not have MPC.
Treatment
The results of sensitive tests for C. trachomatis or N. gonorrhoeae (e.g., culture or nucleic acid amplification tests) should determine the need for treatment, unless the likelihood of infection with either organism is high or the patient is unlikely to return for treatment. Empiric treatment should be considered for a patient who has a suspected case of gonorrhea and/or chlamydia if a) the prevalence of these diseases differs substantially (i.e., greater than 15%) between clinics in the geographic area and b) the patient might be difficult to locate for treatment. After the possibilities of relapse and reinfection have been excluded, management of persistent MPC is unclear. For such cases, additional antimicrobial therapy may be of little benefit.
Follow-Up
Follow-up should be as recommended for the infections for which the woman is being treated. If symptoms persist, women should be instructed to return for reevaluation and to abstain from sexual intercourse even if they have completed the prescribed therapy.
Management of Sex Partners
Management of sex partners of women treated for MPC should be appropriate for the identified or suspected STD. Partners should be notified, examined, and treated for the STD identified or suspected in the index patient.
Patients should be instructed to abstain from sexual intercourse until they and their sex partners are cured. Because a microbiologic test of cure usually is not recommended, patients should abstain from sexual intercourse until therapy is completed (i.e., 7 days after a single-dose regimen or after completion of a 7-day regimen).
Special Considerations
HIV Infection
Patients who have MPC and also are infected with HIV should receive the same treatment regimen as those who are HIV-negative.
Chlamydial Infection
In the United States, chlamydial genital infection occurs frequently among sexually active adolescents and young adults. Asymptomatic infection is common among both men and women. Screening sexually active adolescents for chlamydial infection should be routine during annual examinations, even if symptoms are not present. Screening women aged 20-24 years also is suggested, particularly for those who have new or multiple sex partners and who do not consistently use barrier contraceptives.
Chlamydial Infection in Adolescents and Adults
Several important sequelae can result from C. trachomatis infection in women; the most serious of these include PID, ectopic pregnancy, and infertility. Some women who have apparently uncomplicated cervical infection already have subclinical upper reproductive tract infection. A recent investigation of patients in a health maintenance organization demonstrated that screening and treatment of cervical infection can reduce the likelihood of PID.
Treatment
Treatment of infected patients prevents transmission to sex partners; and, for infected pregnant women, treatment might prevent transmission of C. trachomatis to infants during birth. Treatment of sex partners helps to prevent reinfection of the index patient and infection of other partners.
Coinfection with C. trachomatis often occurs among patients who have gonococcal infection; therefore, presumptive treatment of such patients for chlamydia is appropriate (see Gonococcal Infection, Dual Therapy for Gonococcal and Chlamydial Infections). The following recommended treatment regimens and the alternative regimens cure infection and usually relieve symptoms.
Recommended Regimens
Azithromycin 1 g orally in a single dose,
OR
Doxycycline 100 mg orally twice a day for 7 days.
Alternative Regimen
Erythromycin base 500 mg orally four times a day for 7 days,
OR
Erythromycin ethylsuccinate 800 mg orally four times a day for 7 days,
OR
Ofloxacin 300 mg orally twice a day for 7 days.
The results of clinical trials indicate that azithromycin and doxycycline are equally efficacious. These investigations were conducted primarily in populations in which follow-up was encouraged and adherence to a 7-day regimen was good. Azithromycin should always be available to health-care providers to treat at least those patients for whom compliance is in question.
In populations with erratic health-care-seeking behavior, poor compliance with treatment, or minimal follow-up, azithromycin may be more cost-effective because it provides single-dose, directly observed therapy. Doxycycline costs less than azithromycin, and it has been used extensively for a longer period. Erythromycin is less efficacious than either azithromycin and doxycycline, and gastrointestinal side effects frequently discourage patients from complying with this regimen. Ofloxacin is similar in efficacy to doxycycline and azithromycin, but it is more expensive to use and offers no advantage with regard to the dosage regimen. Other quinolones either are not reliably effective against chlamydial infection or have not been adequately evaluated.
To maximize compliance with recommended therapies, medications for chlamydial infections should be dispensed on site, and the first dose should be directly observed. To minimize further transmission of infection, patients treated for chlamydia should be instructed to abstain from sexual intercourse for 7 days after single-dose therapy or until completion of a 7-day regimen. Patients also should be instructed to abstain from sexual intercourse until all of their sex partners are cured to minimize the risk for reinfection.
Follow-Up
Patients do not need to be retested for chlamydia after completing treatment with doxycycline or azithromycin unless symptoms persist or reinfection is suspected, because these therapies are highly efficacious. A test of cure may be considered 3 weeks after completion of treatment with erythromycin. The validity of chlamydial culture testing at less than 3 weeks after completion of therapy to identify patients who did not respond to therapy has not been established. False-negative results can occur because of small numbers of chlamydial organisms. In addition, nonculture tests conducted at less than 3 weeks after completion of therapy for patients who were treated successfully could be false-positive because of continued excretion of dead organisms.
Some studies have demonstrated high rates of infection among women retested several months after treatment, presumably because of reinfection. In some populations (e.g., adolescents), rescreening women several months after treatment might be effective for detecting further morbidity.
Management of Sex Partners
Patients should be instructed to refer their sex partners for evaluation, testing, and treatment. Because exposure intervals have received limited evaluation, the following recommendations are somewhat arbitrary. Sex partners should be evaluated, tested, and treated if they had sexual contact with the patient during the 60 days preceding onset of symptoms in the patient or diagnosis of chlamydia. Health-care providers should treat the most recent sex partner even if the time of the last sexual contact was greater than 60 days before onset or diagnosis.
Patients should be instructed to abstain from sexual intercourse until they and their sex partners have completed treatment. Because a microbiologic test of cure usually is not recommended, abstinence should be continued until therapy is completed (i.e., 7 days after a single-dose regimen or after completion of a 7-day regimen). Timely treatment of sex partners is essential for decreasing the risk for reinfecting the index patient.
Special Considerations
Pregnancy
Doxycycline and ofloxacin are contraindicated for pregnant women. The safety and efficacy of azithromycin use in pregnant and lactating women have not been established. Repeat testing, preferably by culture, 3 weeks after completion of therapy with the following regimens is recommended, because a) none of these regimens are highly efficacious and b) the frequent side effects of erythromycin might discourage patient compliance with this regimen.
Recommended Regimens for Pregnant Women
Erythromycin base 500 mg orally four times a day for 7 days,
OR
Amoxicillin 500 mg orally three times a day for 7 days.
Alternative Regimens for Pregnant Women
Erythromycin base 250 mg orally four times a day for 14 days,
OR
Erythromycin ethylsuccinate 800 mg orally four times a day for 7 days,
OR
Erythromycin ethylsuccinate 400 mg orally four times a day for 14 days,
OR
Azithromycin 1 g orally in a single dose.
Note: Erythromycin estolate is contraindicated during pregnancy because of drug-related hepatotoxicity. Preliminary data indicate that azithromycin may be safe and effective. However, data are insufficient to recommend the routine use of azithromycin in pregnant women.
HIV Infection
Patients who have chlamydial infection and also are infected with HIV should receive the same treatment regimen as those who are HIV-negative.
Chlamydial Infection in Infants
Prenatal screening of pregnant women can prevent chlamydial infection among neonates. Pregnant women who are less than 25 years of age or who have new or multiple sex partners particularly should be targeted for screening. Periodic prevalence surveys of chlamydial infection can be conducted to confirm the validity of using these recommendations in specific clinical settings.
C. trachomatis infection of neonates results from perinatal exposure to the mother's infected cervix. The prevalence of C. trachomatis infection among pregnant women usually is greater than 5%, regardless of race/ethnicity or socioeconomic status. Neonatal ocular prophylaxis with silver nitrate solution or antibiotic ointments does not prevent perinatal transmission of C. trachomatis from mother to infant. However, ocular prophylaxis with those agents does prevent gonoccocal ophthalmia and should be continued for that reason (see Prevention of Ophthalmia Neonatorum).
Initial C. trachomatis perinatal infection involves mucous membranes of the eye, oropharynx, urogenital tract, and rectum. C. trachomatis infection in neonates is most often recognized by conjunctivitis that develops 5-12 days after birth. Chlamydia is the most frequent identifiable infectious cause of ophthalmia neonatorum. C. trachomatis also is a common cause of subacute, afebrile pneumonia with onset from 1 to 3 months of age. Asymptomatic infections also can occur in the oropharynx, genital tract, and rectum of neonates.
Ophthalmia Neonatorum Caused by C. trachomatis
A chlamydial etiology should be considered for all infants aged less than or equal to 30 days who have conjunctivitis.
Diagnostic Considerations
Sensitive and specific methods used to diagnose chlamydial ophthalmia in the neonate include both tissue culture and nonculture tests (e.g., direct fluorescent antibody tests and immunoassays). Giemsa-stained smears are specific for C. trachomatis, but such tests are not sensitive. Specimens must contain conjunctival cells, not exudate alone. Specimens for culture isolation and nonculture tests should be obtained from the everted eyelid using a dacron-tipped swab or the swab specified by the manufacturer's test kit. A specific diagnosis of C. trachomatis infection confirms the need for treatment not only for the neonate, but also for the mother and her sex partner(s). Ocular exudate from infants being evaluated for chlamydial conjunctivitis also should be tested for N. gonorrhoeae.
Recommended Regimen
Erythromycin 50 mg/kg/day orally divided into four doses daily for 10-14 day
Topical antibiotic therapy alone is inadequate for treatment of chlamydial infection and is unnecessary when systemic treatment is administered.
Follow-Up
The efficacy of erythromycin treatment is approximately 80%; a second course of therapy may be required. Follow-up of infants to determine resolution is recommended. The possibility of concomitant chlamydial pneumonia should be considered.
Management of Mothers and Their Sex Partners
The mothers of infants who have chlamydial infection and the sex partners of these women should be evaluated and treated (see Chlamydial Infection in Adolescents and Adults).
Infant Pneumonia Caused by C. trachomatis
Characteristic signs of chlamydial pneumonia in infants include a) a repetitive staccato cough with tachypnea and b) hyperinflation and bilateral diffuse infiltrates on a chest radiograph. Wheezing is rare, and infants are typically afebrile. Peripheral eosinophilia sometimes occurs in infants who have chlamydial pneumonia. Because clinical presentations differ, initial treatment and diagnostic tests should encompass C. trachomatis for all infants aged 1-3 months who possibly have pneumonia.
Diagnostic Considerations
Specimens for chlamydial testing should be collected from the nasopharynx. Tissue culture is the definitive standard for chlamydial pneumonia; nonculture tests can be used with the knowledge that nonculture tests of nasopharyngeal specimens produce lower sensitivity and specificity than nonculture tests of ocular specimens. Tracheal aspirates and lung biopsy specimens, if collected, should be tested for C. trachomatis.
The microimmunofluorescence test for C. trachomatis antibody is useful but not widely available. An acute IgM antibody titer greater than or equal to 1:32 is strongly suggestive of C. trachomatis pneumonia.
Because of the delay in obtaining test results for chlamydia, the decision to include an agent in the antibiotic regimen that is active against C. trachomatis must frequently be based on the clinical and radiologic findings. The results of tests for chlamydial infection assist in the management of an infant's illness and determine the need for treating the mother and her sex partner(s).
Recommended Regimen
Erythromycin base 50 mg/kg/day orally divided into four doses daily for 10-14 days.
Follow-Up
The effectiveness of erythromycin treatment is approximately 80%; a second course of therapy may be required. Follow-up of infants is recommended to determine whether the pneumonia has resolved. Some infants with chlamydial pneumonia have had abnormal pulmonary function tests later in childhood.
Management of Mothers and Their Sex Partners
Mothers of infants who have chlamydial infection and the sex partners of these women should be evaluated and treated according to the recommended treatment of adults for chlamydial infections (see Chlamydial Infection in Adolescents and Adults).
Infants Born to Mothers Who Have Chlamydial Infection
Infants born to mothers who have untreated chlamydia are at high risk for infection; however, prophylatic antibiotic treatment is not indicated, and the efficacy of such treatment is unknown. Infants should be monitored to ensure appropriate treatment if infection develops.
Chlamydial Infection in Children
Sexual abuse must be considered a cause of chlamydial infection in preadolescent children, although perinatally transmitted C. trachomatis infection of the nasopharynx, urogenital tract, and rectum may persist for greater than 1 year (see Sexual Assault or Abuse of Children). Because of the potential for a criminal investigation and legal proceedings for sexual abuse, a diagnosis of C. trachomatis in a preadolescent child requires the high specificity provided by isolation in cell culture. The cultures should be confirmed by microscopic identification of the characteristic intracytoplasmic inclusions, preferably by fluorescein-conjugated monoclonal antibodies specific for C. trachomatis.
Diagnostic Considerations
Nonculture tests for chlamydia should not be used because of the possibility of false-positive test results. With respiratory tract specimens, false-positive results can occur because of cross-reaction of test reagents with Chlamydia pneumoniae; with genital and anal specimens, false-positive results occur because of cross-reaction with fecal flora.
Recommended Regimens
Children who weigh less than 45 kg:
Erythromycin base 50 mg/kg/day orally divided into four doses daily for 10-14 days.
NOTE: The effectiveness of treatment with erythromycin is approximately 80%; a second course of therapy may be required.
Children who weigh less than or equal to 45 kg but are less than 8 years of age:
Azithromycin 1 g orally in a single dose.
Children less than or equal to 8 years of age:
Azithromycin 1 g orally in a single dose,
OR
Doxycycline 100 mg orally twice a day for 7 days.
Other Management Considerations
See Sexual Assault or Abuse of Children.
Follow-Up
Follow-up cultures are necessary to ensure that treatment has been effective.
Gonococcal Infection
Gonococcal Infection in Adolescents and Adults
In the United States, an estimated 600,000 new infections with N. gonorrhoeae occur each year. Most infections among men produce symptoms that cause them to seek curative treatment soon enough to prevent serious sequelae -- but this may not be soon enough to prevent transmission to others. Many infections among women do not produce recognizable symptoms until complications (e.g., pelvic inflammatory disease {PID}) have occurred. Both symptomatic and asymptomatic cases of PID can result in tubal scarring that leads to infertility or ectopic pregnancy. Because gonococcal infections among women often are asymptomatic, an important component of gonorrhea control in the United States continues to be the screening of women at high risk for STDs.
Dual Therapy for Gonococcal and Chlamydial Infections
Patients infected with N. gonorrhoeae often are coinfected with C. trachomatis; this finding led to the recommendation that patients treated for gonococcal infection also be treated routinely with a regimen effective against uncomplicated genital C. trachomatis infection. Routine dual therapy without testing for chlamydia can be cost-effective for populations in which chlamydial infection accompanies 20%-40% of gonococcal infections, because the cost of therapy for chlamydia (e.g., $0.50-$1.50 for doxycycline) is less than the cost of testing. Some experts believe that the routine use of dual therapy has resulted in substantial decreases in the prevalence of chlamydial infection. Because most gonococci in the United States are susceptible to doxycycline and azithromycin, routine cotreatment might hinder the development of antimicrobial-resistant N. gonorrhoeae.
Since the introduction of dual therapy, the prevalence of chlamydial infection has decreased in some populations, and simultaneous testing for chlamydial infection has become quicker, more sensitive, and more widely available. In geographic areas in which the rates of coinfection are low, some clinicians might prefer to test for chlamydia rather than treat presumptively. However, presumptive treatment is indicated for patients who may not return for test results.
Quinolone-Resistant N. gonorrhoeae (QRNG)
Cases of gonorrhea caused by N. gonorrhoeae resistant to fluoroquinolones have been reported sporadically from many parts of the world, including North America, and are becoming widespread in parts of Asia. As of February 1997, however, QRNG occurred rarely in the United States: less than 0.05% of 4,639 isolates collected by CDC's Gonococcal Isolate Surveillance Project (GISP) during 1996 had minimum inhibitory concentrations (MICs) greater than or equal to 1.0 ug/mL to ciprofloxacin. The GISP sample is collected from 26 cities and includes approximately 1.3% of all reported gonococcal infections among men in the United States. As long as QRNG strains comprise less than 1% of all N. gonorrhoeae strains isolated at each of the 26 cities, the fluoroquinolone regimens can be used with confidence. However, importation of QRNG will probably continue, and the prevalence of QRNG in the United States could increase to the point that fluoroquinolones no longer reliably eradicate gonococcal infections.
Uncomplicated Gonococcal Infections of the Cervix, Urethra, and Rectum
Recommended Regimens
Cefixime 400 mg orally in a single dose,
OR
Ceftriaxone 125 mg IM in a single dose,
OR
Ciprofloxacin 500 mg orally in a single dose,
OR
Ofloxacin 400 mg orally in a single dose,
PLUS
Azithromycin 1 g orally in a single dose,
OR
Doxycycline 100 mg orally twice a day for 7 days.
Cefixime has an antimicrobial spectrum similar to that of ceftriaxone, but the 400-mg oral dose does not provide as high nor as sustained a bactericidal level as that provided by the 125-mg dose of ceftriaxone. In published clinical trials, the 400-mg dose cured 97.1% of uncomplicated urogenital and anorectal gonococcal infections. The advantage of cefixime is that it can be administered orally.
Ceftriaxone in a single injection of 125 mg provides sustained, high bactericidal levels in the blood. Extensive clinical experience indicates that ceftriaxone is safe and effective for the treatment of uncomplicated gonorrhea at all sites, curing 99.1% of uncomplicated urogenital and anorectal infections in published clinical trials.
Ciprofloxacin is effective against most strains of N. gonorrhoeae. At a dose of 500 mg, ciprofloxacin provides sustained bactericidal levels in the blood; in published clinical trials, it has cured 99.8% of uncomplicated urogenital and anorectal infections. Ciprofloxacin is safe, relatively inexpensive, and can be administered orally.
Ofloxacin also is effective against most strains of N. gonorrhoeae, and it has favorable pharmacokinetics. The 400-mg oral dose has been effective for treatment of uncomplicated urogenital and anorectal infections, curing 98.4% of infections in published clinical trials.
Alternative Regimens
Spectinomycin 2 g IM in a single dose. Spectinomycin is expensive and must be injected; however, it has been effective in published clinical trials, curing 98.2% of uncomplicated urogenital and anorectal gonococcal infections. Spectinomycin is useful for treatment of patients who cannot tolerate cephalosporins and quinolones.
Single-dose cephalosporin regimens other than ceftriaxone 125 mg IM and cefixime 400 mg orally that are safe and highly effective against uncomplicated urogenital and anorectal gonococcal infections include a) ceftizoxime 500 mg IM, b) cefotaxime 500 mg IM, c) cefotetan 1 g IM, and d) cefoxitin 2 g IM with probenecid 1 g orally. None of these injectable cephalosporins offers any advantage in comparison with ceftriaxone, and clinical experience with these regimens for treatment of uncomplicated gonorrhea is limited.
Single-dose quinolone regimens include enoxacin 400 mg orally, lomefloxacin 400 mg orally, and norfloxacin 800 mg orally. These regimens appear to be safe and effective for the treatment of uncomplicated gonorrhea, but data regarding their use are limited. None of the regimens appears to offer any advantage over ciprofloxacin at a dose of 500 mg or ofloxacin at 400 mg.
Many other antimicrobials are active against N. gonorrhoeae; however, these guidelines are not intended to be a comprehensive list of all effective treatment regimens. Azithromycin 2 g orally is effective against uncomplicated gonococcal infection, but it is expensive and causes gastrointestinal distress too often to be recommended for treatment of gonorrhea. At an oral dose of 1 g, azithromycin is insufficiently effective, curing only 93% of patients in published studies.
Uncomplicated Gonococcal Infection of the Pharynx
Gonococcal infections of the pharynx are more difficult to eradicate than infections at urogenital and anorectal sites. Few antigonococcal regimens can reliably cure such infections greater than 90% of the time.
Although chlamydial coinfection of the pharynx is unusual, coinfection at genital sites sometimes occurs. Therefore, treatment for both gonorrhea and chlamydia is suggested.
Recommended Regimens
Ceftriaxone 125 mg IM in a single dose,
OR
Ciprofloxacin 500 mg orally in a single dose,
OR
Ofloxacin 400 mg orally in a single dose,
PLUS
Azithromycin 1 g orally in a single dose,
OR
Doxycycline 100 mg orally twice a day for 7 days.
Follow-Up
Patients who have uncomplicated gonorrhea and who are treated with any of the recommended regimens need not return for a test of cure. Patients who have symptoms that persist after treatment should be evaluated by culture for N. gonorrhoeae, and any gonococci isolated should be tested for antimicrobial susceptibility. Infections identified after treatment with one of the recommended regimens usually result from reinfection rather than treatment failure, indicating a need for improved patient education and referral of sex partners. Persistent urethritis, cervicitis, or proctitis also may be caused by C. trachomatis and other organisms.
Management of Sex Partners
Patients should be instructed to refer sex partners for evaluation and treatment. All sex partners of patients who have N. gonorrhoeae infection should be evaluated and treated for N. gonorrhoeae and C. trachomatis infections if their last sexual contact with the patient was within 60 days before onset of symptoms or diagnosis of infection in the patient. If a patient's last sexual intercourse was greater than 60 days before onset of symptoms or diagnosis, the patient's most recent sex partner should be treated. Patients should be instructed to avoid sexual intercourse until therapy is completed and they and their sex partners no longer have symptoms.
Special Considerations
Allergy, Intolerance, or Adverse Reactions
Persons who cannot tolerate cephalosporins or quinolones should be treated with spectinomycin. Because spectinomycin is unreliable (i.e., only 52% effective) against pharyngeal infections, patients who have suspected or known pharyngeal infection should have a pharyngeal culture evaluated 3-5 day
Pregnancy
Pregnant women should not be treated with quinolones or tetracyclines. Those infected with N. gonorrhoeae should be treated with a recommended or alternate cephalosporin. Women who cannot tolerate a cephalosporin should be administered a single 2-g dose of spectinomycin IM. Either erythromycin or amoxicillin is recommended for treatment of presumptive or diagnosed C. trachomatis infection during pregnancy (see Chlamydial Infection).
HIV Infection
Patients who have gonococcal infection and also are infected with HIV should receive the same treatment regimen as those who are HIV-negative.
Gonococcal Conjunctivitis
Only one study of the treatment of gonococcal conjunctivitis among adults in North America has been published recently. In that study, 12 of 12 patients responded favorably to a single 1-g IM injection of ceftriaxone. The following recommendations reflect the opinions of expert consultants.
Treatment
Recommended Regimen
Ceftriaxone 1 g IM in a single dose, and lavage the infected eye with saline solution once.
Management of Sex Partners
Patients should be instructed to refer their sex partners for evaluation and treatment (see Gonococcal Infection, Management of Sex Partners).
Disseminated Gonococcal Infection (DGI)
DGI results from gonococcal bacteremia. DGI often results in petechial or pustular acral skin lesions, asymmetrical arthralgia, tenosynovitis, or septic arthritis. The infection is complicated occasionally by perihepatitis, and rarely by endocarditis or meningitis. Strains of N. gonorrhoeae that cause DGI tend to cause minimal genital inflammation. In the United States, these strains have occurred infrequently during the past decade.
No studies of the treatment of DGI among persons in North America have been published recently. The following recommendations reflect the opinions of experts. No treatment failures have been reported.
Treatment
Hospitalization is recommended for initial therapy, especially for patients who cannot be relied on to comply with treatment, for those in whom the diagnosis is uncertain, and for those who have purulent synovial effusions or other complications. Patients should be examined for clinical evidence of endocarditis and meningitis. Patients treated for DGI should be treated presumptively for concurrent C. trachomatis infection unless appropriate testing excludes this infection.
Recommended Initial Regimen
Ceftriaxone 1 g IM or IV every 24 hours.
Alternative Initial Regimens
Cefotaxime 1 g IV every 8 hours,
OR
Ceftizoxime 1 g IV every 8 hours,
OR
For persons allergic to B-lactam drugs:
Ciprofloxacin 500 mg IV every 12 hours,
OR
Ofloxacin 400 mg IV every 12 hours,
OR
Spectinomycin 2 g IM every 12 hours. All regimens should be continued for 24-48 hours after improvement begins, at which time therapy may be switched to one of the following regimens to complete a full week of antimicrobial therapy:
Cefixime 400 mg orally twice a day,
OR
Ciprofloxacin 500 mg orally twice a day,
OR
Ofloxacin 400 mg orally twice a day.
Management of Sex Partners
Gonococcal infection often is asymptomatic in sex partners of patients who have DGI. As with uncomplicated gonococcal infections, patients should be instructed to refer their sex partners for evaluation and treatment (see Gonococcal Infection, Management of Sex Partners).
Gonococcal Meningitis and Endocarditis
Recommended Initial Regimen
Ceftriaxone 1-2 g IV every 12 hours.
Therapy for meningitis should be continued for 10-14 days; therapy for endocarditis should be continued for at least 4 weeks. Treatment of complicated DGI should be undertaken in consultation with an expert.
Management of Sex Partners
Patients should be instructed to refer their sex partners for evaluation and treatment (see Gonococcal Infection, Management of Sex Partners).
Gonococcal Infection in Infants
Gonococcal infection usually results from exposure to infected cervical exudate at birth. It is usually an acute illness that becomes manifest 2-5 days after birth. The prevalence of infection among infants depends on the prevalence of infection among pregnant women, on whether pregnant women are screened for gonorrhea, and on whether newborns receive ophthalmia prophylaxis.
The most serious manifestations of N. gonorrhoeae infection in newborns are ophthalmia neonatorum and sepsis, including arthritis and meningitis. Less serious manifestations include rhinitis, vaginitis, urethritis, and inflammation at sites of fetal monitoring.
Ophthalmia Neonatorum Caused by N. gonorrhoeae
Although N. gonorrhoeae is a less frequent cause of ophthalmia neonatorum in the United States than C. trachomatis and nonsexually transmitted agents, it is especially important because it may result in perforation of the globe of the eye and in blindness.
Diagnostic Considerations
Infants at increased risk for gonococcal ophthalmia are those who do not receive ophthalmia prophylaxis and those whose mothers have had no prenatal care or whose mothers have a history of STDs or substance abuse. Gonococcal ophthalmia is strongly suggested when typical Gram-negative diplococci are identified in conjunctival exudate, justifying presumptive treatment for gonorrhea after appropriate cultures for N. gonorrhoeae are obtained. Appropriate chlamydial testing should be done simultaneously. Presumptive treatment for N. gonorrhoeae may be indicated for newborns who are at increased risk for gonococcal ophthalmia and who have conjunctivitis but do not have gonococci in a Gram-stained smear of conjunctival exudate.
In all cases of neonatal conjunctivitis, conjunctival exudate should be cultured for N. gonorrhoeae and tested for antibiotic susceptibility before a definitive diagnosis is made. A definitive diagnosis is important because of the public health and social consequences of a diagnosis of gonorrhea. Nongonococcal causes of neonatal ophthalmia include Moraxella catarrhalis and other Neisseria species that are indistinguishable from N. gonorrhoeae on Gram-stained smear but can be differentiated in the microbiology laboratory.
Recommended Regimen
Ceftriaxone 25-50 mg/kg IV or IM in a single dose, not to exceed 125 mg.
NOTE: Topical antibiotic therapy alone is inadequate and is unnecessary if systemic treatment is administered.
Other Management Considerations
Simultaneous infection with C. trachomatis should be considered when a patient does not respond satisfactorily to treatment. Both mother and infant should be tested for chlamydial infection at the same time that gonorrhea testing is done (see Ophthalmia Neonatorum Caused by C. trachomatis). Ceftriaxone should be administered cautiously to hyperbilirubinemic infants, especially those born prematurely.
Follow-Up
Infants who have gonococcal ophthalmia should be hospitalized and evaluated for signs of disseminated infection (e.g., sepsis, arthritis, and meningitis). One dose of ceftriaxone is adequate therapy for gonococcal conjunctivitis, but many pediatricians prefer to continue antibiotics until cultures are negative at 48-72 hours. The duration of therapy should be decided in consultation with experienced physicians.
Management of Mothers and Their Sex Partners
The mothers of infants who have gonococcal infection and the mothers' sex partners should be evaluated and treated according to the recommendations for treating gonococcal infections in adults (see Gonococcal Infection in Adolescents and Adults).
Disseminated Gonococcal Infection and Gonococcal Scalp Abscess in Newborns
Sepsis, arthritis, meningitis, or any combination of these are rare complications of neonatal gonococcal infection. Localized gonococcal infection of the scalp might result from fetal monitoring through scalp electrodes. Detection of gonococcal infection in neonates who have sepsis, arthritis, meningitis, or scalp abscesses requires cultures of blood, CSF, and joint aspirate on chocolate agar. Specimens obtained from the conjunctiva, vagina, oropharynx, and rectum that are cultured on gonococcal selective medium are useful for identifying the primary site(s) of infection, especially if inflammation is present. Positive Gram-stained smears of exudate, CSF, or joint aspirate provide a presumptive basis for initiating treatment for N. gonorrhoeae. Diagnoses based on Gram-stained smears or presumptive identification of cultures should be confirmed with definitive tests on culture isolates.
Recommended Regimens
Ceftriaxone 25-50 mg/kg/day IV or IM in a single daily dose for 7 days, with a duration of 10-14 days if meningitis is documented;
OR
Cefotaxime 25 mg/kg IV or IM every 12 hours for 7 days, with a duration of 10-14 days if meningitis is documented.
Prophylactic Treatment for Infants Whose Mothers Have Gonococcal Infection
Infants born to mothers who have untreated gonorrhea are at high risk for infection.
Recommended Regimen in the Absence of Signs of Gonococcal Infection
Ceftriaxone 25-50 mg/kg IV or IM, not to exceed 125 mg, in a single dose.
Other Management Considerations
Mother and infant should be tested for chlamydial infection.
Follow-Up
A follow-up examination is not required.
Management of Mothers and Their Sex Partners
The mothers of infants who have gonococcal infection and the mothers' sex partners should be evaluated and treated according to the recommendations for treatment of gonococcal infections in adults (see Gonococcal Infection).
Gonococcal Infection in Children
After the neonatal period, sexual abuse is the most frequent cause of gonococcal infection in preadolescent children (see Sexual Assault or Abuse of Children). Vaginitis is the most common manifestation of gonococcal infection in preadolescent children. PID following vaginal infection is probably less common than among adults. Among sexually abused children, anorectal and pharyngeal infections with N. gonorrhoeae are common and frequently asymptomatic.
Diagnostic Considerations
Because of the legal implications of a diagnosis of N. gonorrhoeae infection in a child, only standard culture procedures for the isolation of N. gonorrhoeae should be used for children. Nonculture gonococcal tests for gonococci (e.g., Gram-stained smear, DNA probes, and EIA tests) should not be used alone; none of these tests have been approved by FDA for use with specimens obtained from the oropharynx, rectum, or genital tract of children. Specimens from the vagina, urethra, pharynx, or rectum should be streaked onto selective media for isolation of N. gonorrhoeae, and all presumptive isolates of N. gonorrhoeae should be identified definitively by at least two tests that involve different principles (e.g., biochemical, enzyme substrate, or serologic). Isolates should be preserved to enable additional or repeated testing.
Recommended Regimens for Children Who Weigh greater than or equal to 45 kg
Children who weigh greater than or equal to 45 kg should be treated with one of the regimens recommended for adults (see Gonococcal Infection).
NOTE: Quinolones are not approved for use in children because of concerns about toxicity based on animal studies. However, investigations of ciprofloxacin treatment in children who have cystic fibrosis demonstrated no adverse effects.
Recommended Regimen for Children Who Weigh less than 45 kg and Who Have Uncomplicated Gonococcal Vulvovaginitis, Cervicitis, Urethritis, Pharyngitis, or Proctitis
Ceftriaxone 125 mg IM in a single dose.
Alternative Regimen
Spectinomycin 40 mg/kg (maximum dose: 2 g) IM in a single dose may be used, but this therapy is unreliable for treatment of pharyngeal infections. Some experts use cefixime to treat gonococcal infections in children because it can be administered orally; however, no reports have been published concerning the safety or effectiveness of cefixime used for this purpose.
Recommended Regimen for Children Who Weigh less than 45 kg and Who Have Bacteremia or Arthritis
Ceftriaxone 50 mg/kg (maximum dose: 1 g) IM or IV in a single dose daily for 7 days.
Recommended Regimen for Children Who Weigh less than or equal to 45 kg and Who Have Bacteremia or Arthritis
Ceftriaxone 50 mg/kg (maximum dose: 2 g) IM or IV in a single dose daily for 10-14 days.
Follow-Up
Follow-up cultures are unnecessary if ceftriaxone is used. If spectinomycin is used to treat pharyngitis, a follow-up culture is necessary to ensure that treatment was effective.
Other Management Considerations
Only parenteral cephalosporins are recommended for use in children. Ceftriaxone is approved for all gonococcal infections in children; cefotaxime is approved for gonococcal ophthalmia only. Oral cephalosporins used for treatment of gonococcal infections in children have not been evaluated adequately.
All children who have gonococcal infections should be evaluated for coinfection with syphilis and C. trachomatis. For a discussion of concerns regarding sexual assault, refer to Sexual Assault or Abuse of Children.
Ophthalmia Neonatorum Prophylaxis
Instillation of a prophylactic agent into the eyes of all newborn infants is recommended to prevent gonococcal ophthalmia neonatorum; this procedure is required by law in most states. All the recommended prophylactic regimens in this section prevent gonococcal ophthalmia. However, the efficacy of these preparations in preventing chlamydial ophthalmia is less clear, and they do not eliminate nasopharyngeal colonization by C. trachomatis. The diagnosis and treatment of gonococcal and chlamydial infections in pregnant women is the best method for preventing neonatal gonococcal and chlamydial disease. Not all women, however, receive prenatal care; and ocular prophylaxis is warranted because it can prevent sight-threatening gonococcal ophthalmia and it is safe, easy to administer, and inexpensive.
Prophylaxis
Recommended Regimens
Silver nitrate (1%) aqueous solution in a single application,
OR
Erythromycin (0.5%) ophthalmic ointment in a single application,
OR
Tetracycline ophthalmic ointment (1%) in a single application.
One of these recommended preparations should be instilled into both eyes of every neonate as soon as possible after delivery. If prophylaxis is delayed (i.e., not administered in the delivery room), a monitoring system should be established to ensure that all infants receive prophylaxis. All infants should be administered ocular prophylaxis, regardless of whether delivery is vaginal or cesarian. Single-use tubes or ampules are preferable to multiple-use tubes. Bacitracin is not effective. Povidone iodine has not been studied adequately.
