This is a corrected version of the article that appeared in print.
Am Fam Physician. 2000;61(2):379-386
The Centers for Disease Control and Prevention updated its guidelines for the treatment of sexually transmitted diseases. The guidelines include the following information: recommendations for hepatitis A immunization and expanded indications for hepatitis B vaccination; updated diagnostic criteria for pelvic inflammatory disease and parenteral treatment regimens; information on two additional antiviral agents for the treatment of genital herpes; a recommendation for use of a single 1-g dose of azithromycin (Zithromax) to treat urethritis and chlamydial cervicitis; information on the use of quinolones in the treatment of gonococcal infections; information on podofilox and imiquimod, which are both patient-applied medications, in the treatment of noncervical human papillomavirus infection; updated guidelines for the prevention and detection of congenital syphilis; and information on how to prevent the spread of sexually transmitted diseases by educating patients about the importance of changing their sexual behaviors. To have a significant impact on the current rate of transmission of sexually transmitted diseases, family physicians should develop a plan to integrate the guidelines into their practices.
Family physicians have a crucial role in the prevention and treatment of sexually transmitted diseases (STDs). This role is particularly important because of the increasing incidence of some STDs despite efforts to educate patients and the general public.1 The 1998 Centers for Disease Control and Prevention (CDC) guidelines for the treatment of STDs update the 1993 report and provide direction in the diagnosis, treatment and prevention of this class of infections.2,3
Hepatitis B
Hepatitis B virus (HBV) continues to be a significant public health issue. Sexual transmission still accounts for 30 to 60 percent of the estimated 240,000 new cases of HBV infection reported each year.1 The risk of perinatal transmission from mothers who are positive for hepatitis B surface antigen and hepatitis B e antigen to untreated infants may be as high as 85 percent. This issue is significant because approximately 90 percent of infected infants progress to chronic HBV infection. Even if infants are not infected at birth, children of infected mothers are at higher risk of contracting HBV infection during the first five years of life. No specific treatments for acute HBV infection exist and, while recombinant alfa-2b interferon (Intron A) and lamivudine (Epivir) are now available for treatment of chronic HBV infection, they are only about 40 percent effective in eliminating HBV.4
MANAGEMENT
Immunization is a key component of the guidelines and is combined with targeted screening of all pregnant patients.3 Hepatitis B immune globulin (HBIG; Hep-B-Gamma-gee) will prevent approximately 75 percent of HBV infections in sexual partners of HBV-infected patients, and its use is recommended in conjunction with initiation of the vaccine series. However, HBIG must be given as soon as possible after exposure; its effectiveness seven days after exposure is unknown. The vaccine is administered in three doses, with the first two doses given at least one month apart. The third dose should be given at least four months after the initial immunization. If the series is interrupted, the next dose should be given as soon as possible, and the series should then continue. It is not necessary to restart the three-dose series. Because human immunodeficiency virus (HIV) infection can impair a patient's response to the vaccine, post-vaccination serology (hepatitis B surface antibody) should be obtained in HIV-infected patients. Post-vaccination serology is also recommended for sexual contacts of persons with chronic HBV and infants of women with chronic HBV infection. The recommended categories of persons who should receive routine HBV immunization (Table 1) are expanded in the updated CDC guidelines.3
| All infants and children |
| Sexually active homosexual and bisexual men |
| Sexually active heterosexual men and women who have or have had another STD or more than one sexual partner in the past 6 months, or are prostitutes |
| Illegal drug users (injected and noninjected drugs) |
| Health care workers |
| Recipients of certain blood products |
| Household and sexual contacts of persons with chronic HBV infection |
| Adoptees from countries in which HBV infection is endemic |
| Certain international travelers |
| Clients and employees of facilities for the develop-mentally disabled |
| Hemodialysis patients |
Hepatitis A
A discussion of hepatitis A virus (HAV) and recommendations for the management of the disease are new to the 1998 CDC guidelines. In 1995, the category of patients with the highest rate of HAV transmission was household and sexual contacts.3 Currently, no treatment is available for acute HAV infection except supportive therapy.
MANAGEMENT
The new CDC guidelines recommend immunization of people at risk for exposure to HAV.3 Passive immunization with immune globulin, given within 14 days after exposure, will prevent over 85 percent of new HAV infections. The immunization is effective for three to six months and is recommended for pre-and postexposure prophylaxis of household and sexual contacts. Passive immunization is not recommended for patients who have received at least one dose of hepatitis A vaccine more than one month before exposure.
Two hepatitis A vaccines (Havrix, Vaqta) are presently available; they are given in a two-dose series six months apart.5 Vaccine recipients have a 99 to 100 percent rate of response to the first dose, while the second dose provides long-term immunity. The vaccine series is recommended as preexposure prophylaxis for men who have sex with men and for users of illegal injected drugs if local outbreaks of the infection have occurred in these populations. Vaccination is also recommended for persons with chronic hepatitis C infection.
Pelvic Inflammatory Disease
Pelvic inflammatory disease (PID) consists of a variety of ascending infections that affect the upper female reproductive tract. Approximately 10 percent of women will develop PID during their reproductive years, and a significant number will have complications from the infection.6 The most common agents that cause PID are gonorrhea and Chlamydia, but other micro-organisms can also cause the condition.
DIAGNOSIS
Often PID goes undiagnosed because some cases are asymptomatic and others have mild or nonspecific signs or symptoms. To reduce the potential for missed diagnosis of PID and subsequent damage to the reproductive tract, diagnostic criteria for the initiation of empiric treatment have been established (Table 2).3 In women who are sexually active and at risk of infection, empiric treatment should be initiated if all three of the minimal criteria are met. The additional criteria can be used to support the diagnosis of PID. Establishing definitive criteria for the diagnosis of PID is only justified in a few select cases.
| Minimal criteria* |
| Lower abdominal tenderness |
| Adnexal tenderness |
| Cervical motion tenderness |
| Additional criteria |
| Oral temperature > 38.3°C (101°F) |
| Abnormal cervical or vaginal discharge |
| Elevated erythrocyte sedimentation rate |
| Elevated C-reactive protein level |
| Laboratory documentation of cervical infection with Neisseria gonorrhoeae or Chlamydia trachomatis |
| Definitive criteria |
| Histopathologic evidence of endometritis on endometrial biopsy |
| Transvaginal sonography or other imaging modes showing thickened fluid-filled tubes with or without free pelvic fluid or tubo-ovarian complex |
| Laparoscopic abnormalities consistent with PID |
MANAGEMENT
| Surgical emergencies (e.g., appendicitis) cannot be excluded |
| Pregnancy |
| No clinical response to oral antimicrobial therapy |
| Inability to follow or tolerate an outpatient oral regimen |
| Severe illness, high fever, or nausea and/or vomiting |
| Presence of tubo-ovarian abscess |
| Immunodeficiency |
The treatment guidelines contain five different parenteral regimens for the treatment of PID (Table 4).3 Infusion of doxycycline (Vibramycin) can cause discomfort, which can be reduced by adding a short-acting local anesthesia, heparin or steroids to the infusion. Because the bioavailability of parenteral and oral doxycycline is similar, oral therapy should be used whenever possible. Parenteral therapy may be changed to oral therapy 24 hours after the patient shows clinical improvement.
| Regimen A | ||
| Cefotetan (Cefotan), 2 g IV every 12 hours | ||
| or | ||
| Cefoxitin (Mefoxin), 2 g IV every 6 hours | ||
| plus | ||
| Doxycycline (Vibramycin), 100 mg IV or orally every 12 hours | ||
| Regimen B | ||
| Clindamycin, 900 mg IV every 8 hours | ||
| plus | ||
| Gentamicin, IV or IM, loading dose 2 mg per kg, followed by maintenance dose, 1.5 mg per kg, every 8 hours. Single daily dosing may be substituted. | ||
| Alternative regimens | ||
| 1. Ofloxacin (Floxin), 400 mg IV every 12 hours | ||
| plus | ||
| Metronidazole (Flagyl), 500 mg IV every 8 hours | ||
| or | ||
| 2. Ampicillin/sulbactam (Unasyn), 3 g IV every 6 hours | ||
| plus | ||
| Doxycycline, 100 mg IV or orally every 12 hours | ||
| or | ||
| 3. Ciprofloxacin (Cipro), 200 mg IV every 12 hours | ||
| plus | ||
| Doxycycline 100 mg IV or orally every 12 hours | ||
| plus | ||
| Metronidazole 500 mg IV every 8 hours | ||
Various outpatient treatment regimens for PID are listed in Table 5.3 The full course of treatment lasts 14 days.3 A regimen of amoxicillin-clavulanic acid (Augmentin) plus doxycycline has been shown to be effective in the treatment of PID, but because this regimen has gastrointestinal side effects, its overall success might be limited. Azithromycin (Zithromax) has been evaluated in the treatment of PID, but the data are insufficient to currently recommend this agent in any of the treatment regimens.
| Regimen A | ||
| Ofloxacin (Floxin), 400 mg orally twice a day for 14 days | ||
| plus | ||
| Metronidazole (Flagyl), 500 mg twice a day for 14 days | ||
| Regimen B* | ||
| 1. Ceftriaxone (Rocephin), 250 mg IM once or 2. Cefoxitin (Mefoxin), 2 g IM plus Probenecid (Benemid), 1 g orally, in a single concurrent dose or 3. Another parenteral third-generation cephalosporin (e.g., ceftrizoxine [Cefizox] or cefotaxime [Claforan]) plus Doxycycline (Vibramycin), 100 mg orally twice a day for 14 days | ||
Genital Herpes
It is estimated that up to 45 million persons in the United States have genital herpes, and most of them have not been diagnosed because their disease is mild or asymptomatic. Because of the significant risk of perinatal transmission of genital herpes, the CDC continues to recommend cesarean sections for women in labor who have active disease, particularly if it is a primary infection.3
MANAGEMENT
The updated guidelines for the treatment of genital herpes include two new antiviral drugs, famciclovir (Famvir) and valacyclovir (Valtrex), in addition to established therapy with acyclovir (Zovirax).3 Antiviral therapy may decrease the severity and duration of a genital herpes outbreak.7 Treatment of recurrent episodes is most effective if started within one day of the appearance of symptoms. Suppressive therapy reduces the frequency of recurrence by up to 75 percent in persons who have six or more recurrences per year and also reduces asymptomatic viral shedding between outbreaks.8,9 Continuous suppressive therapy with the new antiviral agents has been shown to be safe for up to two years, and with acyclovir, for up to six years.3 Even so, efforts should be made to stop suppressive therapy after one year to reassess the frequency of recurrence, because the natural course of the disease exhibits decreasing frequency of recurrences over time. Intravenous antiviral drugs, including cidofovir (Vistide) and foscarnet (Foscavir), are also available but should be reserved for use in patients with severe or complicated infections.
Urethritis and Cervicitis
The diagnosis and treatment of urethritis and cervicitis are discussed in detail in the new CDC guidelines. The changes in these guidelines consist of a newer etiologic agent and new treatment regimens.3
NONGONOCOCCAL URETHRITIS
Mycoplasma genitalium is a new etiologic agent added to the list of bacteria that cause nongonococcal urethritis (NGU). In addition, azithromycin, 1 g orally in a single dose, was Chlamydia trachomatis. added to the list of antibiotic agents recommended for the treatment of NGU. Guidelines for the notification of all sexual contacts of patients with NGU were revised to include any partner who had sexual contact within 60 days of the diagnosis.
RECURRENT OR PERSISTENT URETHRITIS
Two modifications concerning recurrent or persistent urethritis were made to the guidelines. First, empiric treatment for infection with Trichomonas vaginalis was included in the standard treatment regimen. Second, the duration of treatment with erythromycin was shortened from 14 to seven days.
CHLAMYDIAL DISEASE
Three significant changes are included in the guidelines concerning the management of chlamydial infections. First, the recommendation to use sulfisoxazole (Gantrisin) to treat adults and adolescents was deleted. Next, the option to use azithromycin, 1 g orally in a single dose, to treat pregnant women as well as children who weigh more than 45 kg (99 lb) or are eight years of age or older, was added. This regimen may also treat presumed coinfections of Chlamydia and gonorrhea. Finally, the guidelines include the recommendation that infants born to women with untreated chlamydial infections should be monitored closely for symptoms but not treated empirically.
GONOCOCCAL DISEASE
Since the 1993 CDC guidelines were written, quinolones have been included in the treatment options for gonococcal infections. Quinolones are a simple, safe and effective treatment for gonococcal infections of any severity. Ciprofloxacin (Cipro) and ofloxacin (Floxin) can be used intravenously to treat disseminated gonococcal infection and are also available in oral forms. The recommended treatment course is seven days.
One concern about the use of quinolones to treat gonorrhea is the growing resistance of Neisseria gonorrhoeae.10 Although the rate of resistance in the United States is still negligible, the CDC assumes the incidence of that resistance will eventually increase; therefore, the guidelines suggest treatment with a non-quinolone regimen, such as cefixime (Suprax) or ceftriaxone (Rocephin).
Another change in the treatment recommendations for gonococcal disease involves systemic disease in children who weigh more than 45 kg (99 lb). To treat bacteremia, arthritis and meningitis in these children, the guidelines now recommend using the same dosage of ceftriaxone, 50 mg per kg (maximal dose: 2 g) intramuscularly or intravenously once per day for 10 to 14 days.
Noncervical Human Papillomavirus
DIAGNOSIS
Usually, the diagnosis of genital HPV infection can be established through clinical assessment. Biopsy of the lesions can confirm the diagnosis but should be reserved for use in patients in which the diagnosis is uncertain or immunocompromised patients. According to the CDC, no data support the use of viral subtyping of HPV in the routine diagnosis and management of this disease.
MANAGEMENT
The main goal of therapy for noncervical HPV infection is to treat symptomatic visible lesions. There is no evidence that treatment decreases infectivity or changes the natural course of HPV infections or the risk for development of cervical cancer.
The CDC now recommends patient-applied medications to treat HPV.3 The first agent is podofilox (Condylox) 0.5 percent solution or gel. Patients apply the medication to the visible lesions twice a day for three days and then stop treatment for four days. This cycle may be repeated up to four times. The area being treated should not exceed 10 cm2, and the total amount of podofilox used should not exceed 0.5 mL per day. To demonstrate the technique of proper application and to identify which warts to treat, the first dose should be applied by a health care clinician.
Another patient-applied medication is imiquimod (Aldara) 5 percent cream.3 Patients apply the cream to the visible warts at bedtime, three times per week for up to 16 weeks. The treated area should be cleansed with mild soap and water six to 10 hours after application. In the majority of patients, the warts will clear up in eight weeks or less.
The safety of imiquimod and podofilox in pregnant women has not been established. During pregnancy, treatment with trichloroacetic acid or bichloroacetic acid is acceptable.
Intralesional interferon is as effective as the other medications but difficult to administer, and it has a high incidence of adverse systemic effects. Because of these problems, the CDC does not recommend it as a routine treatment for visible HPV lesions.3
Congenital Syphilis
Effective prevention and identification of syphilis in pregnant patients requires routine serology to be performed for all pregnant patients at the time of their first prenatal visit.3 Serologic testing should be repeated, and a sexual history should be taken at 28 weeks of gestation and again at delivery in patients at high risk for contracting syphilis. If a patient has syphilis during pregnancy, her potential for reinfection should be assessed by gathering information about the treatment of her sexual partner. In addition, any pregnant patient with syphilis should be screened for HIV infection.
DIAGNOSIS
An infant born to a seroreactive mother should be evaluated with a quantitative non-treponemal serologic test (e.g., rapid plasma reagin or VDRL). The test must be performed on the infant's serum and not on the blood from the umbilical cord, because the potential for maternal contamination may result in a false-positive test.
Thorough examination of the infant may uncover evidence of congenital syphilis, such as nonimmune hydrops, hepatosplenomegaly, jaundice, rhinitis, skin rash and/or pseudo-paralysis of an extremity. Examination of the placenta or umbilical cord using specific fluorescent antitreponemal antibody staining is recommended, and suspicious lesions or body fluids should also be examined. The need for further evaluation of the infant depends on the presence or absence of physical findings, treatment history of the mother, stage of infection at the time of treatment and comparison of maternal and infant nontreponemal titers at the time of delivery.
MANAGEMENT
The recommended treatment regimen for congenital syphilis is aqueous crystalline penicillin G (Pfizerpen), 100,000 to 150,000 units per kg per day, taken in divided doses every 12 hours for seven days.3 The regimen then shifts to every eight hours for days eight through 10. The alternative regimen is procaine penicillin G (Wycillen), 50,000 units per kg intramuscularly every day for 10 days. Other antibiotic regimens do not have adequate data to support their use in the treatment of congenital syphilis.
Prevention of STDs
A crucial component of the guidelines is the prevention of STDs. Prevention includes the following actions: educating patients at risk for STDs; detecting asymptomatic or symptomatic patients who are unlikely to seek treatment; providing effective diagnosis and treatment of those with STDs; evaluating, treating and counseling the sexual partners of those with STDs; and immunizing patients who are at risk for STDs that are preventable by vaccination.3 Despite the fact that most of the guidelines concentrate on the clinical aspects of STDs, prevention must focus on changing the sexual behaviors of patients at risk.
One step toward prevention is the identification of patients at risk for transmitting or acquiring STDs. Accomplishing this requires taking a thorough sexual history as a part of the routine physical examination. Questions concerning sexual activity need to be asked in a straightforward, nonjudgmental manner.12 Once risk factors have been identified, counseling should be provided with respect and compassion. The prevention message should address the patient's specific high-risk behaviors and include precise information about actions that can be taken to avoid acquiring or transmitting STDs. Optimal preventive messages are “patient-centered,” so that the patient can come to his or her own conclusion about the risks and the behaviors that need to be changed.
As one final preventive measure, any patient diagnosed with any STD should be tested for HIV infection.3 Counseling about the patient's potential risk for contracting HIV or other STDs should be done before and after testing.
Final Comment
The prevention, detection and treatment of STDs are vital components of the family physician's practice. Physicians should integrate the CDC recommendations into their practices. With this step, physicians can significantly affect the reduction of morbidity and mortality related to STDs, as well as decrease the transmission of HIV.