Sexually Transmitted Infections



Sexually Transmitted Infections


Virginia P. Arcangelo



Sexually transmitted infections (STIs) are among the most common illnesses in the world. They have far-reaching health, social, and economic consequences. Our knowledge about the global prevalence and incidence of these infections is limited by the quality and quantity of data available from throughout the world. STIs remain a major public health concern in the United States. The economic burden is impressive: Centers for Disease Control and Prevention’s (CDC) new estimates show that there are about 20 million new infections in the United States each year, with a total of more than 110 million among men and women. STIs cost the American health care system nearly $16 billion in direct medical costs alone (CDC, 2013).

It is estimated that half of all new STIs in the country occur among young men and women. Those at the highest risk for contracting STIs are those between 15 and 24 years, and gay and bisexual men. Gay and bisexual men have the highest rate of syphilis infections. While most STIs will not cause harm, some have the potential to cause serious health problems, especially if not diagnosed and treated early.

In 2015, the CDC updated the guidelines for treating STIs (Table 35.1). Available from the CDC, these guidelines are one of the most widely used documents published by that organization. The guidelines emphasize the development of management strategies that are adaptable to the managed care environment. Because the guidelines are considered the gold standard for treating STIs, most of the information in this chapter is based on them. The goals of therapy for all STIs are to eradicate the causative organism and prevent complications.

The accurate and timely reporting of STIs is integrally important for assessing morbidity trends, targeting limited resources, and assisting local health authorities in partner notification and treatment. STIs, human immunodeficiency virus (HIV), and acquired immunodeficiency syndrome (AIDS) cases should be reported in accordance with state and local statutory requirements. Syphilis, gonorrhea, chlamydia, chancroid, HIV infection, and AIDS are reportable diseases in every state. The requirements for reporting other STIs differ by state, and clinicians should be familiar with state and local reporting requirements. Reporting can be provider or laboratory based.

Intrauterine or perinatally transmitted STIs can have severely debilitating effects on pregnant women, their partners, and their fetuses. All pregnant women and their sex partners should be asked about STIs, counseled about the possibility of perinatal infections, and ensured access to treatment, if needed.

All pregnant women in the United States should be tested for HIV infection as early in pregnancy as possible. Testing should be conducted after the woman is notified that she will be tested for HIV as part of the routine panel of prenatal tests, unless she declines the test.


CHLAMYDIAL INFECTION

Chlamydial infection is the most prevalent STI in the United States, with 2 to 3 million new cases reported annually. The detection and treatment of this disease is important because the complications can be serious.


CAUSES

Chlamydial infection is caused by Chlamydia trachomatis, which shares properties of both bacteria and viruses. The organism is transmitted sexually or perinatally. Repeated infections are common.









TABLE 35.1 Pharmacotherapy for Sexually Transmitted Infections




























































































Infection


Treatment


Comments


Chlamydial infection


azithromycin 1 g PO once or doxycycline 100 mg PO bid for 7 d


Alternative:


Use amoxicillin, erythromycin, or azithromycin in pregnancy.




erythromycin base 500 mg PO qid for 7 d or erythromycin ethylsuccinate 800 mg PO qid for 7 d or ofloxacin 300 mg bid for 7 d or levofloxacin 500 mg PO for 7 d


Genital herpes


Initial episode treatment for 7-10 d


Treatment can be extended if healing is not complete after 10 d.




acyclovir 400 mg PO tid or acyclovir 200 mg PO 5 times a day or valacyclovir 1 g PO bid



Recurrent treatment:




acyclovir 400 mg PO tid for 5 d or acyclovir 800 mg bid for 5 d or acyclovir 800 mg tid for 2 d or famciclovir 125 mg PO bid for 5 d or famciclovir 100 mg bid for 1 d


valacyclovir 500 mg PO bid for 3 d or valacyclovir 1 g once a day for 5 d



Suppressive treatment:




acyclovir 400 mg bid or famciclovir 250 mg bid or valacyclovir 500 mg or 1,000 mg qd


Gonorrhea



ceftriaxone 250 mg IM once PLUS


azithromycin 1 g PO once or doxycycline 100 mg PO bid for 7 d



Alternative:




cefixime 400mg once


Human papillomavirus


Patient applied:


Solution applied with cotton swab and gel with finger to visible warts. This is done for 3 d and then 4 d with no therapy and may be repeated four times.




podofilox 0.5% solution or gel for 3 d and then 4 d of no therapy


imiquimod 5% cream three times a week up to 16 wk



Provider applied:


Area should be washed with mild soap and water 6-10 h after application.


Allow to air-dry. Wash off 1-4 h after application.




podophyllin resin 10%-25% in compound of tincture of benzoin weekly as needed




trichloroacetic acid or bichloracetic acid 80%-90% weekly as needed


Apply only to warts and let dry; white “frosting” appears; powder with talc or sodium bicarbonate to remove unreacted acid.


Pelvic inflammatory disease


ceftriaxone 250 mg IM once or cefoxitin 2 g IM and probenecid 1 g PO once and doxycycline 100 mg PO bid for 14 d


PLUS


doxycycline 100 mg PO bid for 14 d


WITH OR WITHOUT


metronidazole 500 mg PO bid for 14 d


Syphilis


Early primary, secondary, or latent syphilis <1 y




Adult: benzathine penicillin G 2.4 million U, IM single dose


Child: 50,000 U/kg, IM, single dose up to 2.4 mil unit



Latent disease >1 y or unknown duration




Adult: benzathine penicillin G 2.4 million U, IM, for 3 doses at 1-wk intervals


Child: 500,000 U/kg, IM, for 3 doses at 1-wk intervals



Allergic to penicillin and not pregnant: doxycycline 100 mg PO bid for 14 d or tetracycline 500 mg PO bid for 14 d


Allergic to penicillin and pregnant: desensitization followed by treatment with penicillin



From Centers for Disease Control and Prevention. (2006). Sexually transmitted treatment guidelines, 2006. Morbidity and Mortality Weekly Reports, 59 (RR-12), 1-110.



In infants, perinatal exposure to the mother’s cervix causes the infection. The prevalence is greater than 5% regardless of race, ethnicity, or socioeconomic status. In preadolescent children, sexual abuse must be considered as a causative factor for chlamydial infection; infection of the nasopharynx, urogenital tract, and rectum may persist for greater than 1 year. Because criminal investigation is always a possibility, cultures should be confirmed by microscopic fluoroscopy, which can detect conjugated monoclonal antibodies specific for C. trachomatis.

Chlamydial infections occur most frequently in women younger than age 25. All adolescents and young women should be screened for chlamydia yearly, as should any woman who has new or multiple sex partners.



DIAGNOSTIC CRITERIA

The infection may be silent: more than half of infected patients have no clinical signs or symptoms. In symptomatic women, the clinical presentation includes vaginal discharge, mucopurulent cervicitis with edema and friability, urethral syndrome or urethritis, pelvic inflammatory disease (PID), ectopic pregnancy, infertility, and endometritis. Men may report a thin, clear discharge and dysuria. Chlamydial organisms are the major causes of nongonococcal urethritis and epididymitis in young men.

In infants aged 1 to 3 months, chlamydial infection presents in the mucous membranes of the eye, oropharynx, urogenital tract, and rectum and as subacute, afebrile pneumonia; in neonates, it presents as an asymptomatic infection of the oropharynx, genital tract, and rectum. However, chlamydial infection most commonly presents as conjunctivitis 5 to 12 days after birth and is the most frequent identifiable infectious cause of ophthalmia neonatorum. Therefore, for all infants with conjunctivitis who are no older than 30 days, a chlamydial etiology should be considered.

Diagnostic tests for chlamydial ophthalmia neonatorum include tissue cultures and nonculture tests. Ocular exudate should also be tested for Neisseria gonorrhoeae.

Chlamydial infection is diagnosed by examination, culture, and antigen detection methods, including direct fluorescent monoclonal antibody staining, enzyme-linked immunosorbent assay, DNA probe assay, and polymerase chain reaction.


INITIATING DRUG THERAPY

Treatment for all STIs consists of antimicrobial therapy followed by preventive education.


Goals of Drug Therapy

Patients are treated to eradicate the organism and prevent transmission to sex partners or to a newborn during birth. Because chlamydial infections often are accompanied by gonococcal infections, patients may be treated for both infections.


Antibiotic Therapy

Antibiotic treatments are prescribed to cure infection and usually relieve symptoms (CDC, 2015). Azithromycin (Zithromax) and erythromycin (E-Mycin), macrolide antibiotics; doxycycline (Vibramycin), a tetracycline antibiotic; and ofloxacin (Floxin), a fluoroquinolone, are drugs of choice for chlamydial infections.

If therapeutic compliance is in question, azithromycin should be used for treatment because it is prepared as a single-dose drug. Doxycycline, however, has been used more extensively and is less expensive. An alternative regimen can be erythromycin, but it is less efficacious and has gastrointestinal (GI) side effects. Other alternatives include fluoroquinolones such as ofloxacin and levofloxacin (Table 35.2).

In infants, erythromycin base treatment has an efficacy of 80%. A second course of therapy may be required, and follow-up of the infant is recommended.


Mechanism of Action

Azithromycin and erythromycin bind to bacterial ribosomes to block protein synthesis. The drugs are also bactericidal, depending on their concentration. (For more information on antibiotic actions, see Chapter 8.) Doxycycline is thought to act in a similar way, whereas ofloxacin kills bacteria by blocking DNA gyrase and inhibiting DNA synthesis.


Dosages

A single 1-g dose of azithromycin or 100 mg of doxycycline twice a day for 7 days is the usual initial therapy.



Adverse Events

In some patients, GI side effects (nausea, vomiting, diarrhea, abdominal discomfort) cause them to discontinue therapy.









TABLE 35.2 Overview of Drugs Used to Treat Chlamydial Infections*





































































Generic (Trade) Name and Dosage


Selected Adverse Events


Contraindications


Special Considerations


azithromycin (Zithromax)


GI upset, abdominal pain, pseudomembranous colitis, angioedema, cholestatic jaundice


Hypersensitivity to azithromycin, erythromycin, or any macrolide antibiotic


Use with caution with impaired hepatic or renal function.


Do not take with aluminum- or magnesium-containing antacids.



Adult: 1 g PO single dose


Pregnancy: 1 g PO in a single dose


Child (≥45 kg, <8 y): 1 g PO in a single dose


Child (≥8 y): 1 g PO in a single dose (or doxycycline as below)


doxycycline (Vibramycin)


Superinfection, photosensitivity, GI upset, enterocolitis, rash, blood dyscrasias, hepatotoxicity


Pregnancy, lactation, hypersensitivity to any of the tetracyclines


Monitor blood, renal, and hepatic function in long-term use.


Use of drug during tooth development may discolor teeth.


Advise patient to avoid excessive sunlight or ultraviolet light.


Caution patient that drug absorption is reduced when taken with food or bismuth subsalicylate.



Adult: 100 mg bid for 7 d


Child (≥8 y): 100 mg PO bid for 7 d


amoxicillin (Augmentin)


Hypersensitivity reactions, pseudomembranous colitis, GI upset, rash, urticaria, vaginitis


History of Augmentin-associated cholestatic jaundice, hepatic dysfunction, or allergic reactions to any penicillin


Monitor blood, renal, and hepatic function in long-term use.



Pregnancy: 500 mg tid for 7 d


ofloxacin (Floxin)


Rash, hives, rapid heartbeat, difficulty swallowing or breathing, photosensitivity, angioedema, dizziness, light-headedness


Pregnancy, hypersensitivity to ofloxacin or quinolones


Use with caution with hepatic or renal insufficiency.


Do not take with food.


Drink fluids liberally.



300 mg bid for 7 d


levofloxacin (Levaquin)


Same as above


Same as above


Same as above



500 mg daily for 7 d


erythromycin base (E-Mycin)


GI upset, pseudomembranous colitis, hepatic dysfunction, cardiac dysrhythmias, CNS disturbances, urticaria, skin eruptions, hearing loss, superinfection and local irritation


Known hypersensitivity to erythromycin


Prescribe with caution for patients with impaired hepatic function and children who weigh <45 kg.


Effectiveness of treatment is ˜80%; a second course of therapy may be required.


Use for prophylaxis of ophthalmia neonatorum and infant pneumonia.



Adult: 500 mg qid for 7 d


Pregnancy: 500 mg qid for 7 d or 250 mg qid for 14 d


Children: 50 mg/kg/d PO divided into 4 doses daily for 10-14 d


erythromycin ethylsuccinate (E.E.S.)


Same as above


Same as above


Same as above



Adult: 800 mg qid for 7 d


Pregnancy: 800 mg qid for 7 d or 400 mg qid for 14 d





*In adults, pregnant women, children, ophthalmia neonatorum, and infant pneumonia.



Selecting the Most Appropriate Agent

The most appropriate therapy is the one that best matches the needs of the patient in different situations or stages of life. Figure 35.1 and Tables 35.1 and 35.2 summarize treatment options.


Special Population Considerations



Pregnancy

The recommended regimen for pregnancy is a single dose of azithromycin 1 g or amoxicillin 500 mg orally three times daily for 7 days.

Alternative regimens are erythromycin base 250 mg orally four times a day for 14 days, erythromycin ethylsuccinate 800 mg orally four times a day for 7 days or 400 mg orally four times a day for 14 days, or azithromycin 1 g orally, single dose. Erythromycin estolate is contraindicated during pregnancy because of drug-related hepatotoxicity. Doxycycline is contraindicated in the second and third trimester. All pregnant women who have chlamydia should be retested 3 to 4 weeks and then 3 months after their treatment, which is contrary to the discussion in monitoring patient responses. If infection persists, it can severely affect the mother and neonate.


MONITORING PATIENT RESPONSE

Because therapy with azithromycin or doxycycline is highly efficacious, patients do not need to be retested after treatment is completed, unless they are pregnant (see section “Pregnancy”). If alternative agents, such as erythromycin, are used for treatment, repeat testing for cure is no longer recommended unless therapeutic adherence is in question, symptoms persist, or reinfection is suspected (CDC, 2015).

Screening for C. trachomatis should be performed in high-risk groups when the practitioner performs a pelvic examination. High-risk groups include sexually active adolescents and women ages 15 to 24, particularly those who have new or multiple sex partners; those attending family planning clinics, prenatal clinics, or abortion facilities; or those in juvenile detention centers. Screening for high-risk men should be considered when they seek health care.


PATIENT EDUCATION

The patient’s sex partner must be treated. The newest guidelines (CDC, 2015) recommend presumptive treatment for all partners. Patients should abstain from sexual intercourse for 7 days after single-dose therapy or until the 7-day regimen is completed. Abstinence should also continue until the patient’s sex partner has been treated, to prevent reinfection. Sex partners should be treated if they have had sexual contact with the patient during the 60 days preceding onset of symptoms in the patient or the diagnosis of chlamydial infection. The most recent sex partner should be treated even if the time of the last sexual contact was greater than 60 days before onset or diagnosis.



GONORRHEA

Approximately 820,000 new infections with N. gonorrhoeae occur each year in the United States. They are the major causes of PID, tubal scarring, infertility, ectopic pregnancy, and chronic pelvic pain in the United States. Most men seek treatment before serious complications develop, but not soon enough to prevent transmission to others. In women, symptoms may not develop until complications such as PID occur. Screening of men and women at high risk for STIs is an important component of gonorrhea control (CDC, 2015). Patients infected with N. gonorrhoeae frequently are coinfected with C. trachomatis; this finding has led to the recommendation that patients treated for gonococcal infection also be treated routinely with a regimen that is effective against uncomplicated genital C. trachomatis infection. Because the majority of gonococci in the United States are susceptible to doxycycline and azithromycin, routine cotreatment might also hinder the development of antimicrobial-resistant N. gonorrhoeae.


CAUSES

Gonorrhea is caused by N. gonorrhoeae, a gram-negative diplococcal bacterium. It is transmitted by sexual contact, and the rate of male-to-female transmission is higher than female-to-male or male-to-male. Women with gonorrhea have a high prevalence of other STIs, including chlamydial infection, trichomoniasis, bacterial vaginosis, and herpes genitalis.

Uncomplicated anogenital gonorrhea in women can involve the endocervix, urethra, Skene glands, Bartholin glands, and anus. The endocervix is the most common site of infection. Pharyngeal infection can also occur and is usually asymptomatic.



DIAGNOSTIC CRITERIA

In the United States, an estimated 820,000 new N. gonorrhoeae infections 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. Among women, many infections do not produce recognizable symptoms until complications such as PID have occurred. Up to 30% of women with gonorrheal infection have symptoms. Signs and symptoms include purulent or mucopurulent cervical discharge, dysuria, anal bleeding, menorrhagia, and pelvic discomfort. Men may have discharge and regional lymphadenopathy.

Gonorrhea is diagnosed by examination and culture for N. gonorrhoeae. Culture can be obtained from endocervical (women) or urethral (men) swabs, or urine (from both men and women). Diagnosis is confirmed by identification of the organism on culture, positive oxidase reaction, and gram-negative diplococcal morphology on Gram stain.


INITIATING DRUG THERAPY

Preventive education is always offered. Sex partners should be referred for evaluation and treatment of N. gonorrhoeae and C. trachomatis infection if their last contact with the patient was within 60 days before onset of symptoms or diagnosis of infection. The patient’s most recent sex partner should be treated even if the patient’s last sexual intercourse was more than 60 days before onset of the symptoms or diagnosis. All patients diagnosed with gonorrhea should be tested for syphilis.

Patients treated for gonococcal infection are also treated for chlamydial infection because patients with gonorrhea are commonly coinfected with C. trachomatis. The occurrence of fluoroquinolone-resistant N. gonorrhoeae in the United States is rare. Patients with treatment failure should undergo culture and susceptibility testing, and the local health department should be notified (CDC, 2015).


Goals of Drug Therapy

The goal of drug therapy is to eradicate disease and prevent complications and spread of infection to others.


Antibiotics

The CDC describes recommended regimens for uncomplicated gonococcal infections of the cervix, urethra, and rectum (Table 35.3).


Cefixime

Cefixime (Suprax) covers an antimicrobial spectrum similar to that of ceftriaxone (Rocephin). A dose of 400 mg orally once is an alternative therapy to ceftriaxone. The advantage of cefixime is that it can be administered orally, and clinical trials have shown a 97.1% cure rate for uncomplicated urogenital and anorectal gonococcal infections.


Ceftriaxone

A single injection of 250 mg of ceftriaxone provides sustained, high antibacterial levels in the blood. Extensive clinical experience shows that the drug is safe and effective for treating

uncomplicated gonorrhea at all sites, with a cure rate of 99.1% in clinical trials for uncomplicated urogenital and anorectal infections.








TABLE 35.3 Overview of Selected Drugs Used to Treat Uncomplicated Gonococcal Infections in Adults and Children*












































Generic (Trade) Name and Dosage


Selected Adverse Events


Contraindications


Special Considerations


ceftriaxone (Rocephin)


Pseudomembranous colitis, rash, GI upset, hematologic abnormalities


Known allergy to cephalosporins


Prescribe with caution to penicillin-sensitive patients.


Use for uncomplicated gonococcal infection of the pharynx.



Adult: 125 mg IM in a single dose



Child: ophthalmia neonatorum: 25-50 mg/kg IV or IM in a single dose, not to exceed 125 mg


Child: 125 mg IM in a single dose or 50 mg/kg (maximum dose 1 g) IM or IV in a single dose daily for 7 d or 50 mg/kg (maximum dose 2 g) IM or IV in a single dose daily for 10-14 d


Child (<45 kg with bacteremia or arthritis): 50 mg/kg, max 1 g IM or IV in a single daily dose for 7 d


Child (>45 kg with bacteremia or arthritis): 50 mg/kg, max 2 g, IM or IV in a single daily dose for 10-14 d



Prescribe with caution to hyperbilirubinemic infants, especially premature infants.


Prescribe prophylactically in infants whose mothers have gonococcal infection.


cefixime (Suprax)


Pseudomembranous colitis, GI upset, skin rash, headache, dizziness


Known allergy to cephalosporins


Prescribe with caution to penicillin-sensitive patients and patients with renal impairment or GI disease


Prescribe with caution in patients on dialysis



400 mg po in single dose


azithromycin (Zithromax) 2 g PO


GI upset, abdominal pain, pseudomembranous colitis, angioedema, cholestatic jaundice


Hypersensitivity to azithromycin, erythromycin, or any macrolide antibiotic


Prescribe with caution in patients with impaired hepatic or renal function.


Take 1 h before or 2 h after meals for greatest absorption.


Avoid taking with aluminum- or magnesium-containing antacids.


Comes in powder form



Uncomplicated gonococcal infection of the pharynx: 1 g PO in a single dose


doxycycline (Vibramycin) 100 mg PO bid for 7 d


Superinfection, photosensitivity, GI upset, enterocolitis, rash, blood dyscrasias, hepatotoxicity


Pregnancy, lactation, hypersensitivity to any of the tetracyclines


Monitor blood, renal, and hepatic function in long-term use.


Because of photosensitivity, patients should avoid sunlight or UV light.


Use of drug during tooth development may discolor teeth.


Absorption is reduced when drug is taken with food or bismuth subsalicylate (Pepto-Bismol).


Prescribe for uncomplicated gonococcal infection of the pharynx.


*Infections of the cervix, urethra, and rectum; uncomplicated gonococcal infection of the pharynx; ophthalmia neonatorum; and gonococcal infection in children.

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