Treatment for STDs is indicated at time of diagnosis and/or symptom presentation.2 Patients who seek treatment for STDs should be also be screened for HIV infection.2 Goals of therapy include symptom resolution, prevention of disease transmission, and prevention of long-term disease complications. 2,4,7,10,11 For gonorrhea, chlamydia, and syphilis, disease eradication is also a goal of therapy.2,4,7,11 Since genital herpes cannot be eradicated, goals of therapy include viral suppression and decreased frequency and severity of recurrences.2,10 Antimicrobial therapies for individual STDs will be reviewed in this section, however, specific dose and regimen information is presented in Table 29-1.
Treatment Agents for Chlamydia
Azithromycin and doxycycline are the drugs of choice for the treatment of chlamydia. Erythromycin, ofloxacin, and levofloxacin are alternatives. Because azithromycin is administered in a single dose, it may have advantages over doxycycline in patients with compliance difficulties. Erythromycin may be less effective than the azithromycin and doxycycline due to frequency of gastrointestinal side effects associated with its use.2 Because coinfection with C. trachomatis and N. gonorrhoeae commonly occurs, presumptive therapy for gonorrhea should be considered when treating chlamydia.2
Azithromycin and erythromycin, both macrolide antibiotics, work intracellularly by binding to the 23S component of the 50S ribosomal subunit, thereby inhibiting RNA-dependent protein synthesis. Their effects can be bacteriostatic or bactericidal.16 Gastrointestinal side effects such as nausea, vomiting, and diarrhea, can be observed with all macrolides, but are more commonly encountered with erythromycin. Prolongation of the QTc interval also may occur, but is infrequent with azithromycin use. Erythromycin is metabolized by the cytochrome P450 3A4 (CYP 3A4) enzyme system and drug interactions are possible. Azithromycin is associated with fewer drug interactions because it is metabolized by CYP 3A4 to a lesser extent. Azithromycin's long half-life allows less frequent dosing than erythromycin.16
Doxycycline and tetracycline are tetracycline antibiotics that reversibly bind to the 30S bacterial ribosomal subunit, ultimately inhibiting bacterial protein synthesis. This intracellular mechanism of action results in primarily bacteriostatic effects.17 Dose-related gastrointestinal side effects can occur, but are least common with doxycycline. The calcium-binding effects of tetracyclines cause permanent darkening of teeth in children and effects on developing bone. For this reason, tetracyclines are contraindicated in pregnancy (pregnancy category D) and in children under the age of eight.17 Photosensitivity can also occur with the tetracyclines, but can be decreased by using skin protective measures.17 Tetracyclines bind multivalent cations (calcium, aluminum, magnesium, iron, etc.), causing interactions with foods and vitamins that decrease antibiotic absorption. Patients should be instructed to separate cation-containing products from tetracycline antibiotics.17
Ofloxacin and levofloxacin are fluoroquinolone antibiotics that exhibit bactericidal action due to their effects on bacterial DNA. Fluoroquinolones bind and stabilize DNA complexes with topoisomerase II and topoisomerase IV enzymes, causing DNA strand breakage and subsequent cell death.18 Gastrointestinal side effects and CNS effects (dizziness and headache) have been associated with their use.18 Prolongation of the QTc interval can also occur, although generally less frequently than with macrolides. Caution should be used when administering fluoroquinolones with other QTc interval-prolonging drugs.18 Fluoroquinolones have the potential to cause dysglycemia (hypo- or hyperglycemia), and this adverse effect has been most commonly reported in patients with underlying diabetes mellitus.18 Arthropathy and tendon injury may be experienced in specific populations. Arthropathy is most common in patients under 30 years old and presents as joint pain, swelling, and stiffness of the knees.18 Tendon injury generally occurs in older persons and is associated with additional risk factors. Clinical manifestations include severe and sudden pain, most often affecting the Achilles tendon.18 Fluoroquinolones have not adequately been studied in pregnancy (pregnancy category C), and their use is generally discouraged. Fluoroquinolones should not be used as first-line antimicrobial agents in children younger than 18 years of age. Although emerging data suggests these agents can possibly be safely administered to children, extreme caution is advised. Use of fluoroquinolones in children should be limited to life threatening or difficult to treat infections where the benefits of therapy outweigh the risks.18-20
Treatment Agents for Gonorrhea
Therapy for gonococcal urethritis and cervicitis is complicated by the ability of N. gonorrhoeae to develop resistance to antimicrobials.7,8,21,22 Recently, the Centers for Disease Control and Prevention (CDC) revised their treatment recommendations, no longer recommending the use of fluoroquinolones due to the emergence of fluoroquinolone-resistant N. gonorrhoeae.22 Presumptive therapy for chlamydia should be considered when treating gonorrhea since coinfection with C. trachomatis and N. gonorrhoeae is common.2
Currently, cephalosporins represent the only antibiotic class available in the United States that is recommended for the treatment of gonorrhea.22 Along with penicillins, carbapenems, and monobactams, cephalosporins are members of the beta-lactam antibiotic group. Beta-lactams bind and inactivate a family of enzymes, called penicillin-binding proteins, which are required for bacterial cell wall synthesis. This action causes cell death and is bactericidal.23,24 Cephalosporins are generally well tolerated. The potential for cross-allergenicity with cephalosporins exists in patients with penicillin allergy, and is most common with first- and second-generation cephalosporins. While penicillin allergy (hypersensitivity) is reported in up to 10% of the general population, the frequency of a life-threatening reaction (anaphylaxis) is much less (0.01%-0.05%).23
Treatment Agents for Genital Herpes
The antiviral agents recommended for the management of genital herpes are acyclovir, famciclovir, valacyclovir.2 These drugs inhibit viral DNA replication by competitively inhibiting viral DNA polymerase. Subsequent incorporation of the drug into the growing viral DNA chain causes chain termination.25 Famciclovir has a lower affinity for viral DNA polymerase than acyclovir, but has a longer intracellular half-life.25 Valacyclovir is a prodrug of acyclovir that has increased oral bioavailability.25 Acyclovir, famciclovir, and valacyclovir are very well tolerated overall. Neurologic toxicity has been reported with acyclovir and valacyclovir administration due to drug accumulation in renal failure.25
Antiviral therapy does not eradicate latent herpes viral infection, but aids in disease management. Therapy is divided into three approaches: treatment for the initial episode, intermittent therapy for recurrence, and daily suppressive therapy.2 All treatment approaches provide symptom improvement during genital herpes episodes. Daily suppressive therapy also reduces the frequency and severity of recurrences and decreases HSV viral shedding, thereby reducing the risk of disease transmission.2,10 Daily suppressive therapy is associated with an improved quality of life in patients who have frequent recurrences.2 Use of topical antiviral therapy (eg, acyclovir ointment) is discouraged due to limited clinical benefit.2
Treatment Agents for Syphilis
Parenteral penicillin is the drug of choice for syphilis. Tetracyclines and cephalosporins (reviewed earlier) are alternative therapies.2 Penicillins are beta-lactam antimicrobials with the same mechanism of action as cephalosporins.26
Parenteral Penicillin Preparations
Three parenteral penicillin preparations are used for the treatment of syphilis: aqueous crystalline penicillin G, procaine penicillin, and benzathine penicillin G.2 Aqueous crystalline penicillin G is used in the treatment of neurosyphilis and is administered intravenously. Its short half-life necessitates administration every 4 hours or by continuous infusion.26 Procaine penicillin, with the addition of oral probenecid, is an alternative for the treatment of neurosyphilis and is administered intramuscularly. The addition of procaine delays intramuscular drug absorption, allowing for less frequent administration—as infrequently as once daily.26 Benzathine penicillin G is used in the treatment of primary, secondary, latent, and tertiary syphilis. It is administered intramuscularly. Penicillin is released slowly after intramuscular administration of the benzathine preparation, providing sustained concentrations and allowing for single-dose therapy or once weekly dosing.26 Other parenteral penicillin preparations exist, and health care professionals should be aware of their differences in order to avoid mix-ups and inappropriate therapy. The inadvertent administration of a procaine-benzathine penicillin mix (Bicillin C-R) instead of benzathine penicillin (Bicillin L-A) to patients with syphilis has been reported.27 Bicillin C-R contains only half the dose of benzathine penicillin recommended for the treatment of syphilis and is inappropriate therapy for this indication.27 Penicillins are well tolerated, as are other beta-lactam antibiotics. Neither procaine nor benzathine penicillin should be administered intravenously due to the potential for cardiorespiratory arrest and death.26 As mentioned previously, up to 10% of the population reports a penicillin allergy, but life-threatening reactions are much less common. Penicillin desensitization may be considered in certain patients with a confirmed or suspected penicillin allergy who require penicillin therapy.2,23
An acute febrile reaction may occur within hours of initiation of therapy for syphilis.2,11 This reaction, which occurs due to the release of cytokines from dying T. pallidum organisms, is most common in patients with early syphilis. Symptoms such as myalgia, headache, and tachycardia may accompany the fever. The reaction usually subsides within a 24-hour period. Analgesics and antipyretics may provide symptomatic improvement, but have not been shown to be effective for prevention. Complications of the Jarisch-Herxheimer reaction include induction of early labor and fetal distress in pregnant women.11
The treatment of STDs in pregnancy can decrease pregnancy complications and prevent disease transmission to the child.28
Treating pregnant women for chlamydial infection usually prevents transmission to infants during birth.2 Doxycycline and fluoroquinolones should generally be avoided during pregnancy, and azithromycin or amoxicillin (500 mg po tid × 7 days) are recommended.2 Both azithromycin and amoxicillin are classified in pregnancy category B.
Spontaneous abortion, preterm labor, and postpartum infection are associated with untreated N. gonorrhoeae infection. The disease is also transmissible to the newborn, commonly manifesting as a scalp abscess, ophthalmic infection, or disseminated gonococcal disease.28 Cephalosporin treatment is recommended for gonococcal infection during preganancy.2 The recommended cephalosporins are classified in pregnancy category B.
Herpes transmission from an infected mother can cause symptomatic disease in the neonate. The risk of transmission is highest in mothers who have the initial outbreak at the time of delivery. Although a lower risk, transmission also occurs in mothers who have a disease recurrence at the time of delivery. The risk in a mother with recurrent disease but no visible lesions is thought to be low.28 Use of antiviral therapy late in pregnancy decreases herpes recurrences near term as well as transmission to the neonate.28 Acyclovir, famciclovir, and valacyclovir are classified in pregnancy category B.
In addition to transmission during delivery, syphilis can be transmitted in utero during pregnancy. Exposure to syphilis before birth can lead to preterm labor, fetal death, and neonatal infection.28 Penicillin regimens, appropriate for the stage of disease, are recommended for the treatment of syphilis in pregnant women.2 No proven alternatives to penicillin exist for the treatment of syphilis during pregnancy. It is recommended that pregnant patients with a penicillin allergy undergo desensitization and subsequent treatment with penicillin.2
Children, including neonates and infants, who are diagnosed with congenital or acquired STDs should be treated according to guideline recommendations.2 In children who acquire STDs after the neonatal period and for which a nonsexual explanation does not exist, the possibility of sexual abuse and/or assault should be considered.2
In general, pharmacologic treatment for STDs in adolescent patients is the same as in adults. As with adults, appropriate education and counseling on STD risk reduction are important components of the treatment plan.2,29
Because severe or prolonged herpes episodes may occur in immunocompromised patients, doses for patients with HIV infection are typically higher and/or treatment durations longer than in patients who are HIV-negative.2 Treatment guidelines should be consulted for specific recommendations.2 Patients infected with HIV and diagnosed with chlamydia, gonorrhea, or syphilis should be treated in the same manner as patients who are HIV negative.2