Marlon S. Honeywell and Michael D. Thompson
LEARNING OBJECTIVES
Upon completion of the chapter, the reader will be able to:
1. Analyze the behavioral considerations and assess the importance of contraception with regard to the contributing factors of sexually transmitted infections (STIs).
2. Apply the “expedited partner treatment” method when recommending treatment.
3. Identify the patient populations that are epidemiologically affected.
4. Identify causative organisms.
5. Devise a list of the clinical signs and symptoms corresponding to each disease state and classify patients based on recommended criteria.
6. Select appropriate diagnostic procedures.
7. Identify treatment regimens and recommend therapy when appropriate.
8. Design a patient care plan based on the monitoring parameters.
KEY CONCEPTS
Optimal detection and treatment of sexually transmitted diseases depends on counseling by a patient-friendly and knowledgeable clinician who can establish open communication with the patient. Patients, especially adolescents, should be counseled on the importance of using condoms, spermicides, and diaphragms properly.
Generally, when treating a sexually transmitted infection (STI), the patient being treated should be provided with a sufficient quantity of medication for his/her partner also, increasing the probability that the initial infection will be cured in both individuals.
Patients treated for gonorrhea should be assumed to be coinfected with Chlamydia trachomatis; treatment recommendations should cover both organisms. Treatment of Neisseria gonorrhoeae with fluoroquinolones is inadvisable in those with a history of recent foreign travel, infections acquired in California or Hawaii, infections in other areas with increased gonococcal resistance, or in men who have sex with men (MSM).
Parenteral penicillin is the drug of choice for treatment of all stages of syphilis. Though the dose may vary with the stages of syphilis, benzathine penicillin is the drug of choice.
Metronidazole and tinidazole are the standard agents for trichomoniasis; advise patients to avoid the consumption of alcohol during treatment.
Due to the variable appearance of genital warts, treatment may be based on the size, site, and morphology of the lesions. Treatment options include podofilox, imiquimod, podophyllin resin, and bichloro-and trichloroacetic acid.
Acyclovir, valacyclovir, and famciclovir may be prescribed to treat first and intermittent episodes of genital herpes and to suppress active herpetic infections.
Bacterial vaginosis (BV) is caused by overgrowth of anaerobic organisms and may be treated with oral or intravaginal metronidazole or intravaginal clindamycin.
In patients with pelvic inflammatory disease (PID), resolution of infection (i.e., N. gonorrhoeae, C. trachomatis, Streptococcus spp., and gram-negative facultative bacteria) and mitigation of sequelae should be the main goal of pharmacologic therapy.
Approximately 10% of persons who have chancroid acquired in the United States are coinfected with Treponema pallidum or herpes simplex virus.
Though we have made progress in medicine, age-old problems of infectious disease continue to plague us.1 Even with the discovery of newly improved antibiotics, few sexually transmitted infections (STIs) have been completely eradicated. Many have reemerged secondary to modern social trends of sexual activity, and some as a result of the HIV epidemic, socioeconomic concerns, and the global lack of preventive education. Educating the public decreases the probability of infection in some individuals; however, this tactic alone may not be sufficient. Optimal detection and treatment of sexually transmitted diseases depends on counseling by a patient-friendly and knowledgeable clinician who can establish open communication with the patient.
BEHAVIORAL CONSIDERATIONS
The correlation between risky sexual behavior and STIs is well documented.2 Inconsistent and incorrect condom use has been recognized to increase the incidence of new STIs. Assuming that patients, especially adolescents, consistently use and understand how to use condoms, spermicides, or diaphragms can be detrimental and may contribute to nonpharmacologic mismanagement.3 Health care providers who manage persons at risk for STIs should counsel women concerning the option for emergency contraception, if indicated, and provide it in a timely fashion if desired by the woman. Plan B (two 750 mcg levonorgestrol) has been approved in the United States for the prevention of unintended pregnancy.4
In addition to the increasing number of adolescents engaging in unsafe sexual practices is a high incidence of men who have sex with men (MSM) and women who have sex with women (WSW). Many MSM do not disclose their HIV status. This “don’t ask, don’t tell” practice has been linked to an upsurge in newly diagnosed HIV infections and STIs among previously noninfected people.5 Although limited data are available with regard to STIs in WSW, risk of transmission probably varies by the specific STI and sexual techniques. Sharing penetrative items or employing practices involving digital vaginal or digital anal contact most likely represent common modes of transmission. This possibility is supported by reports of metronidazole-resistant trichomoniasis and genotype-specific HIV transmitted sexually between women who reported such behaviors and an increased prevalence of bacterial vaginosis (BV) among monogamous WSW.6
Optimally, both sex partners should be treated simultaneously for a STI; however, this is difficult to accomplish. Clinics and health departments often proactively attempt dual treatment by providing a prescription for the partner to the index patient (the patient who is evaluated by a clinician), a practice commonly known as expedited partner treatment.
GONORRHEA
Gonorrhea is a curable STI caused by the gram-negative diplococcus Neisseria gonorrhoeae. Proper therapeutic management with antimicrobial agents is essential to eradicate this infection and prevent the development of associated sequelae such as a urethritis, cervicitis, or dysuria.
In the United States, the highest rate of gonococcal infection is seen within the 15- to 24-year-old age groups for both sexes; although more cases are reported in men. Approximately 600,000 new cases occur annually in the United States.7 Factors associated with an increased risk of infection include ethnicity, low socioeconomic status, and illicit drug use. The risk of a cervical infection after a single episode of vaginal intercourse is approximately 50% and increases with multiple exposures. Furthermore, rates of reinfection are significantly higher among ethnic minorities.
PATHOPHYSIOLOGY
Attachment to mucosal epithelium, mediated in part by pili and Opa (outer membrane opacity proteins), is followed by penetration of N. gonorrhoeae through epithelial cells to the submucosal tissue within 24 to 48 hours. A vigorous response by neutrophils begins with sloughing of the epithelium, development of submucosal microabscesses, and exudation of pus. Stained smears usually reveal large numbers of gonococci within a few neutrophils, whereas most cells contain no organisms.8
DIAGNOSIS
Several laboratory tests are available to aid in the diagnosis of gonorrhea and include gram-stained smears, culture, or the DNA hybridization probe. A gram stain of a male urethral specimen that demonstrates polymorphonuclear leukocytes with intracellular gram-negative diplococci may be considered diagnostic in symptomatic men. A gram-negative stain should not be considered sufficient for ruling out infection in asymptomatic men.4 All patients who test positive for gonorrhea should be tested for other STIs, including chlamydia, syphilis, and HIV.
Clinical Presentation of Gonorrhea7,9
General
• Purulent discharge
Signs
• Painful or swollen testicles
• Tubal scarring
Symptoms
Men:
• May be asymptomatic, though acute urethritis is the predominant manifestation
• Urethral discharge and dysuria, usually without urinary frequency or urgency
• When compared with nongonococcal urethritis, the discharge in gonococcal urethritis is generally more profuse and purulent
• Pain during urination
Women:
• Cervicitis, urethritis, increased vaginal discharge, dysuria and intermenstrual bleeding
• Pain during urination
• Abdominal pain
Patient Encounter 1, Part 1
KL is a 27-year-old African American female who visits a clinic complaining of profuse urethral discharge for the past several days. She also informs the nurse that she did not have a menstrual cycle last month and that a home pregnancy test taken this morning revealed that she was indeed pregnant. The patient admits to having sexual intercourse without barrier contraception (condoms) with her boyfriend within the past week or two and is not sure of other sexual encounter(s) in which he may have been involved.
What information is suggestive of gonorrhea?
What potential risk factors for STIs are present?
What impact will pregnancy have on diagnostic and treatment plans for STI management?
TREATMENT
Desired Outcome
The desired outcome is complete eradication of N. gonorrhoeae and avoidance of sequelae.
Pharmacologic Therapy4,9,10
Patients infected with gonorrhea often are coinfected with Chlamydia trachomatis and should receive therapy to eradicate both organisms concurrently. While fluoroquinolones and broad-spectrum cephalosporins have been effective in the treatment of gonorrhea, resistant strains of N. gonorrhoeae have still emerged. In the far-eastern countries, as many as 50% of gonococcal strains exhibit decreased susceptibility to fluoroquinolones. Though ciprofloxacin is still an option for treatment, gonococcal resistance to ciprofloxacin is usually indicative of its resistance to other fluoroquinolones. As a result, monitoring for fluoroquinolone resistance is now essential to ensure proper treatment and to ascertain the maximum time that this class may be employed as a treatment option.
Fluoroquinolones should not be prescribed for infections in MSM, or in those with a history of recent foreign travel or partners’ travel, infections acquired in California or Hawaii, or infections in other areas with increased gonococcal resistance.11
Patient Encounter 1, Part 2
PMH: Currently receiving no medications; no prior history of STIs; no drug allergies noted
FH: Noncontributory
SH: Admits to having unprotected sex with boyfriend. Does not smoke or drink alcohol
ROS: C/o vaginal discharge, recent nonpruritic rash development across abdominal area noted over past 3 to 5 days
PE:
VS: BP 130/80 mm Hg, P 70 bpm, T 37°C (98.6°F)
Lab: Urethral discharge swab revealed N. gonorrhoeae; rapid plasma reagin (RPR) test was positive.
Given this additional information, what is your assessment of the patient’s condition?
What consideration should be given to other STIs?
Identify your treatment goals for this patient.
What pharmacologic alternatives are available for this patient?
Treatment of gonorrhea may vary according to clinical presentation and is indicated as follows:
Uncomplicated Gonococcal Infection of the Cervix, Urethra, and Rectum*: Ceftriaxone 125 mg intramuscularly or ciprofloxacin 500 mg orally or cefixime 400 mg orally or levofloxacin 250 mg orally plustreatment for chlamydial infection if it has not been ruled out.
MSM or Heterosexuals With a History of Recent Travel*: Ceftriaxone 125 mg intramuscularly or cefixime 400 mg orally plus treatment for chlamydial infection if it has not been ruled out.
Uncomplicated Gonococcal Infection of the Pharynx*: Ceftriaxone 125 mg intramuscularly or ciprofloxacin 500 mg orally plus treatment for chlamydial infection if it has not been ruled out.
MSM or Heterosexuals With a History of Recent Travel*: Ceftriaxone 125 mg intramuscularly plus treatment for chlamydial infection if it has not been ruled out.
Coverage for Coinfection With Chlamydia trachomatis: Azithromycin 1 g orally as a single dose or doxycycline 100 mg orally twice daily for 7 days.
*Regimens are given for one dose only.
Patient Encounter 1, Part 3
Unprotected sex is a major risk factor for contracting STIs. Although the purulent discharge is consistent with gonorrhea infection, a positive urethral swab coupled with an incubation period consistent with gonorrhea confirms the diagnosis. A serologic test for syphilis should be performed on all pregnant women at the first prenatal visit and a RPR should be performed at the time pregnancy is confirmed and treatment provided. Although the patient has confirmed gonorrhea, infection with Chlamydia trachomatis occurs commonly in this setting. Additionally, pregnant patients should be tested for this infection during the first prenatal visit and treated appropriately. Further, the presence of a rash could possibly suggest that the patient may have contracted syphilis previously, potentially indicative of secondary syphilis.
If this patient had an allergy to penicillin, how would the therapeutic management of the identified problems change?
Treatment of Gonorrhea in Special Situations
Uncomplicated infections of the cervix, urethra, and rectum can be treated with one of the following regimens in adults:
Recommendations During Pregnancy:
• Ceftriaxone 125 mg intramuscularly as a single dose plus therapy recommended for coinfection with Chlamydia
• Spectinomycin 2 g intramuscularly as a single dose plus therapy recommended for coinfection with Chlamydia
• Doxycycline and fluoroquinolones are contraindicated
Recommendations for Disseminated Gonococcal Infection (Regimens Should Be Continued for 24 to 48 Hours): Ceftriaxone 1 g intramuscularly or IV every 24 hours or cefotaxime 1 g IV every 8 hours orceftizoxime 1 g IV every 8 hours or levofloxacin 250 mg IV every 24 hours or spectinomycin 2 g intramuscularly every 12 hours
After improvement begins, therapy is then switched to one of the following 7-day oral regimens: Cefixime 400 mg orally twice daily or ciprofloxacin 500 mg orally twice daily or levofloxacin 500 mg orally once daily.
Uncomplicated Infections of the Cervix, Urethra, and Rectum in Children Less Than 45 kg: Ceftriaxone 125 mg intramuscularly as a single dose or spectinomycin 40mg/kg intramuscularly as a single dose orceftriaxone 50 mg/kg intramuscularly or IV once daily for 7 days in children with bacteremia or arthritis.
Gonococcal Conjunctivitis: Ceftriaxone 1 g intramuscularly once for adults or ceftriaxone 25 to 50 mg/kg IV or intramuscularly as a single dose for ophthalmia neonatorum or infants born to mothers with gonococcal infection as prophylaxis.
Ophthalmic Neonatorum or Prophylactic Treatment for Infants Whose Mothers Have Gonococcal Infection: Ceftriaxone 25 to 50 mg/kg IV or intramuscularly in a single dose, not to exceed 125 mg.
Ophthalmic Neonatorum Prophylaxis: Erythromycin (0.5%) ophthalmic ointment in a single application to the eyes or tetracycline (1%) ophthalmic ointment in a single application to the eyes.
PATIENT CARE AND MONITORING
Monitoring is generally not required.
CHLAMYDIA
EPIDEMIOLOGY
Infection with C. trachomatis has increased dramatically in recent years. This bacterium is the most common cause of nongonococcal urethritis, accounting for as many as 50% of cases. The prevalence is highest in individuals lesser than or equal to 25 years. Associated sequelae include pelvic inflammatory disease (PID), ectopic pregnancy, and infertility.
PATHOPHYSIOLOGY
C. trachomatis possesses characteristics resembling both bacteria and viruses. Its major membrane is comparable to that of gram-negative bacteria, although it lacks a peptidoglycan cell wall and requires cellular components from the host for replication. Chlamydia transmission risk is thought to be less than that of gonorrhea.
DIAGNOSIS
Common tests used to diagnose C. trachomatis include culture, the enzyme immunoassay, the DNA hybridization probe, or the direct fluorescent monoclonal antibody test. Diagnosis has been confirmed in women through urine or swab specimen collected from the endocervix and in men using a urethral swab or urine specimen. Most women are asymptomatic; therefore, an annual screening or physical is necessary, as early detection may reduce rates of transmission.
TREATMENT12
Uncomplicated Urethral, Endocervical, or Rectal Infection in Adults: The recommended adult regimen is azithromycin 1 g orally in a single dose or doxycycline 100 mg orally twice daily for 7 days. An alternate regimen iserythromycin ethylsuccinate 800 mg orally four times daily for 7 days or erythromycin base 500 mg orally four times daily for 7 days or levofloxacin 500 mg orally once daily for 7 days.
Clinical Presentation of Chlamydia10
General
• Asymptomatic
Signs
• Beefy red cervix that bleeds easily (women)
Symptoms
• When present, the urethral discharge is watery and less purulent than that seen with acute gonococcal urethritis. Complications resulting from lack of treatment or inadequate treatment include: epididymitis (in males), and PID including associated complications in women.
Other Diagnostic Tests
• Culture is usually positive for both chlamydia and gonorrhea.
The recommended regimen for pregnancy is azithromycin 1 g orally in a single dose or amoxicillin 1 g orally in a single dose or amoxicillin 500 mg orally three times daily for 7 days.
Alternate regimens include erythromycin base 500 mg orally four times daily for 7 days or 250 mg orally four times daily for 14 days or erythromycin ethylsuccinate 800 mg orally four times daily for 7 days or 400 mg orally four times daily for 14 days.
C. trachomatis Infection in Infants: Treatment of ophthalmia neonatorum or infant pneumonia should be with erythromycin base or ethylsuccinate 50 mg/kg/day orally divided into four doses daily for 14 days.
PATIENT CARE AND MONITORING
Monitoring is generally not required.
SYPHILIS
Syphilis, attributed to the spirochete Treponema pallidum, can have numerous and complex manifestations. Clinician familiarity, stage-specific diagnosis, and effective treatment are vital. Missed or inappropriately treated syphilis may result in cardiovascular complications, neurologic disease, or congenital syphilis.
EPIDEMIOLOGY
Since the 1940s, the incidence of syphilis declined drastically following the introduction of penicillin, but rose when HIV arrived from obscurity in the 1980s. In 2000, the rate of primary and secondary syphilis in the United States was 2.1 cases per 100,000 population. From 2001 to 2004, the rate increased to 2.7, primarily as a result of increases in cases among MSM. The 2006 morbidity and mortality report also reflects a substantial increase of syphilis among black men, emphasizing the need for enhanced preventive measures among blacks and MSM. The disparity among men and women has been observed across racial and ethnic groups and is highest in the South and among non-Hispanic blacks.13
PATHOPHYSIOLOGY
T. pallidum rapidly penetrates intact mucous membranes or microscopic dermal abrasions, and within a few hours, enters the lymphatics and blood to produce systemic illness. During the secondary stage, examinations commonly demonstrate abnormal findings in the cerebrospinal fluid (CSF). As the infection progresses, the parenchyma of the brain and spinal cord may subsequently be damaged.
Stages of Syphilis
Primary Syphilis
Usually manifests as a solitary, painless chancre. Primary syphilis develops at the site of infection approximately 3 weeks after exposure to T. pallidum; the chancre is highly infectious.14
Secondary Syphilis
Without appropriate treatment, primary syphilis will advance to secondary syphilis, a stage usually apparent from its clinical symptomatology. Symptoms include fatigue, diffuse rash, fever, lymphadenopathy, and genital or perineal condyloma latum. Also, the skin is most often affected and a rash may present as macular, macropapular, or pustular lesions, or involve skin surfaces including the palms of the hands and soles of the feet.
Patient Encounter 2
KG is an HIV-positive male who complains of the appearance of a “sore” on his penis. He reports having unprotected sexual intercourse with another male approximately 5 to 7 days prior to the appearance of the lesion. He denies pain or itching at the site of the lesion, dysuria, or frequent urination. Additionally, there appears to be no vesicles in the genital area.
What information is suggestive of syphilis?
What potential risk factors for STIs are present?
How should the diagnosis of syphilis be confirmed in this patient?
If the diagnosis of syphilis is confirmed, what therapeutic options exist for this patient?
Latent Syphilis
Early Latent. Involves the first year after infection and may be established in patients who have seroconverted in the past year, who have had symptoms of primary or secondary syphilis in the past year, or who have had sex with a partner with primary, secondary, or latent syphilis in the past year.
Late Latent. Patients should be considered to have late latent syphilis if the aforementioned criteria (early latent) are not met. In both stages, patients are usually asymptomatic and the lesions noted in the primary and secondary phase usually resolve; however, individuals are still seropositive for T. pallidum.
Tertiary Syphilis. Develops years after the initial infection and may involve any organ in the body.
Congenital Syphilis
Congenital syphilis is a condition in which the fetus is infected with T. pallidum as a result of the hematogenous spread from an infected mother, although transmission may also occur from direct contact with the infectious genitalia of the mother. Since the primary stage of syphilis is characterized by spirochetemia, infectious rates of the fetus are nearly 100% if the mother has primary syphilis.15
DIAGNOSIS
Diagnostic procedures include dark-field microscopy,16 nontreponemal exams14 (i.e., the Venereal Disease Laboratory and the rapid plasma reagin [RPR] test), and treponemal exams (i.e., enzyme immunoassay, the T. pallidumhemagglutination test, the fluorescent treponemal antibody test, and the enzyme-linked immunosorbent assay).
TREATMENT
Desired Outcome
After confirming the diagnosis of syphilis, the desired outcome is a fourfold decrease in quantitative nontreponemal titers over a 6-month period and within 12 to 24 months after treatment of latent or late syphilis. An algorithm for the treatment of syphilis is shown in Figure 80–1.
With regard to neurosyphilis, a reduction in neurologic manifestations is desired, which may include seizures, paresis, hyperreflexia, visual disturbances, hearing loss, neuropathy, or loss of bowel and bladder function. In late neurosyphilis, vascular lesions (meningovascular neurosyphilis) may also be observed; thus, a reduction in the number of observed lesions is warranted. A diminution in CSF WBC (less than 10 × 103/mm3 [10 × 109/L]) or protein levels (0.05 g/dL [0.5 g/L]) is also preferred.
Pharmacologic Therapy
Parenterally administered penicillin is recommended for all stages of syphilis (Table 80–1). Although penicillin is the drug of choice, combinations of benzathine penicillin with procaine penicillin or oral penicillin preparations are not considered appropriate treatment regimens. Several reports have demonstrated the misuse of the benzathine–procaine combination (Bicillin C-R) instead of the standard benzathine penicillin (Bicillin L-A).17 Pertinent information related to benzathine penicillin G is found in Table 80–1.
Alternative agents may be used in allergic individuals and include doxycycline, minocycline, tetracycline, or erythromycin base or stearate. Some patients (such as young children or pregnant women) may not respond favorably to alternative modalities or should not receive tetracyclines. Therefore, in patients who must be administered penicillin (i.e., patients who are pregnant or have CNS involvement) or are allergic, desensitization must be performed before the drug is initiated.
Patients may experience fever, chills, tachycardia, and tachypnea, a condition commonly known as the Jarisch-Herxheimer reaction. This reaction is postulated to occur secondary to spiro chete lysis and proinflammatory cytokine cascades. It may transpire as early as 2 hours after penicillin administration and usually resolves within 24 hours. Treatment is supportive and may include antipyretic and anti-inflammatory agents, as well as fluid resuscitation and bed rest.
Primary Syphilis
Drug of Choice
Adults. Benzathine penicillin, 2.4 million units intramuscularly as a single dose.
Children. Benzathine penicillin 50,000 units/kg intramuscularly, up to the adult dose of 2.4 million units in a single dose.
Alternatives
Oral doxycycline 100 mg twice daily for 2 weeks or tetracycline 500 mg by mouth four times daily for 2 weeks. Limited literature also supports the use of ceftriaxone 1 g intramuscularly or IV once daily for 10 days or oral azithromycin as a single 2-g dose.13
Secondary and Early Latent Syphilis
Treatment modalities administered in primary syphilis are also effective in secondary syphilis and early latent syphilis (less than 1 year duration).
Late Latent Syphilis
Benzathine penicillin, 7.2 million units total, administered as three doses of 2.4 million units intramuscularly each at 1-week intervals.
Tertiary Syphilis
Drug of Choice
Benzathine penicillin 2.4 million units administered intramuscularly once weekly for 3 weeks.
Alternatives
In nonpregnant patients with a penicillin allergy, alternative regimens include doxycycline 100 mg orally two times daily for 4 weeks or tetracycline 500 mg orally four times daily for 4 weeks.
FIGURE 80–1. Treatment of syphilis. (CSF, cerebrospinal fluid; IM, intramuscularly.) (From Brown D, Frank J. Diagnosis and Management of Syphilis. Am Fam Physician. 2003;68(2):283–290.) a Alternative treatments for nonpregnant penicillin-allergic patients: doxycycline 100 mg orally twice daily for 2 weeks, or tetracycline 500 mg four times daily for 2 weeks; limited data support ceftriaxone 1 g once daily IM or IV for 8 to 10 days; or azithromycin, 2 g orally (single dose).b Alternative treatments for nonpregnant penicillin-allergic patients: doxycycline, 100 mg orally twice daily for 4 weeks, or tetracycline 500 mg orally four times daily for 4 weeks.
Table 80–1 Benzathine and Procaine Penicillin G Informational Chart
Gummatous and Cardiovascular Syphilis
As long as no evidence of CNS involvement exists, antibiotic therapy for gummatous and cardiovascular syphilis is identical to that for tertiary syphilis.
Neurosyphilis
As an effective treatment for neurosyphilis, the Centers for Disease Control and Prevention (CDC) endorses two regimens of penicillin. Alternatively, ceftriaxone may also be prescribed.18
The regimens of choice are aqueous penicillin G 3 to 4 million units administered IV every 4 hours for 10 to 14 days OR procaine penicillin G 2.4 million units administered intramuscularly once daily, plus probenecid 500 mg orally four times daily, both for 10 to 14 days.
Congenital Syphilis19
The decision to treat an infant should be based on a diagnosis of syphilis in the mother and confirmation of adequacy of maternal treatment. Clinical, laboratory, or radiographic evidence of syphilis in the infant should be documented. Maternal nontreponemal titers (at delivery) should be compared with the infant’s nontreponemal titers. Since diagnosis based on neonatal serologic testing is complicated by the transplacental transfer of maternal IgG antibodies, which can cause a positive test in the absence of infection, neonatal titers are assessed. A titer greater than four times the maternal titer would not generally result from passive transfer and diagnosis is considered confirmed or highly probable.
The following regimens are recommended for treatment of maternal syphilis: benzathine penicillin G 2.4 million units or 7.2 million units intramuscularly over 3 weeks if the duration of syphilis has been at least a year. An alternative regimen is procaine penicillin 0.6 to 0.9 million units intramuscularly for 10 to 14 days, or ceftriaxone 1 g daily intramuscularly or IV for 8 to 10 days.
In women who experience uterine cramping, pelvic pain, or fever, administer acetaminophen to combat these symptoms. Additionally, the patient should be well hydrated and rested.
Treatment of asymptomatic neonates is with 50,000 units/kg of benzathine penicillin G in a single intramuscular dose. Symptomatic neonates should receive 50,000 units/kg of aqueous crystalline penicillin G every 12 hours intramuscularly for the first 7 days of life, then every 8 hours for 3 days, OR procaine penicillin G 50,000 IU/kg intramuscularly as a single dose daily for 10 days.
PATIENT CARE AND MONITORING
The CDC has provided patient care monitoring guidelines for syphilis (Fig. 80–2).4,14,20
Primary and Secondary Syphilis
• After 6, 12, and 24 months of treatment, reexamine the patient and recommend a follow-up quantitative nontreponemal titer. If the patient is asymptomatic, yet has a fourfold increase in nontreponemal titer or persistent or recurrent symptoms are observed, order an HIV test and a lumbar puncture; if the patient is HIV-positive, suggest an infectious disease consult.
FIGURE 80–2. Patient care monitoring for syphilis. (From Brown D, Frank J. Diagnosis and Management of Syphilis. Am Fam Physician. 2003;68(2):283–290.) (a See text for alternative treatment recommendations for nonpregnant penicillin-allergic patients. b See text for treatment recommendations for neurosyphilis.)
• In patients who are both negative for HIV and the lumbar puncture, administer benzathine penicillin G 2.4 million units intramuscularly once weekly for three additional weeks. Perform a patient follow-up in 6 months including a clinical examination and another nontreponemal titer. In HIV-negative patients with lumbar puncture findings compatible with neurosyphilis, treat the patient accordingly for neurosyphilis.
• Six months after the original diagnosis, institute a standard clinical follow-up exam in patients who show no symptomatology and a fourfold decrease in nontreponemal titers. By testing and observing the patient for signs of remission, you may be able to initiate proper treatment or recommend a consult in a timely fashion, thereby decreasing the propensity of the patient’s condition to advance to a higher stage.
Early and Late Latent Syphilis
• Order nontreponemal titers 6, 12, and 24 months after instituting treatment for early or late latent syphilis. Neurosyphilis should be strongly considered in patients who show a fourfold increase in titers, patients who have an initially high titer (1:32 or greater) that fails to decline at least fourfold, HIV-infected patients, and patients who develop signs or symptoms associated with neurosyphilis.
Neurosyphilis
• Follow-up is dependent on the CSF findings. If pleocytosis is present, reexamine the CSF every 6 months until the WBC count normalizes. Consider recommending a second course of treatment if the CSF white count does not decline after 6 months or completely normalize after 2 years.4,14 Failure to normalize may require retreatment; most treatment failures occur in immunocompromised patients.
Congenital Syphilis
• Observe the patient for changes in clinical features; hepatomegaly, jaundice, and bone changes will usually resolve in 3 months.
• Monitor elevated serologic markers (nontreponemal tests) for reduction in titer levels. Given effective treatment, clinical features will usually disappear after 6 months. On this basis, evaluate seropositive infants periodically for at least 6 months.19
TRICHOMONIASIS
Trichomoniasis is caused by the protozoan Trichomonas vaginalis and is far more prevalent than C. trachomatis or N. gonorrhoeae. In the United States, approximately 5 million new cases appear annually, compared with 3 million chlamydial and 650,000 gonococcal cases annually.21
PATHOPHYSIOLOGY
T. vaginalis may be isolated from the vagina, urethra, and Bartholin or Skene glands. After attachment to the host cells, it ignites an inflammatory response exhibited as a discharge containing elevated levels of polymorphonuclear leukocytes. The protozoal pathogen causes direct damage to the epithelium, leading to microulcerations.
DIAGNOSIS
Diagnosis is usually performed with a wet mount or Papanicolaou smear. In women, symptoms are characterized by diffuse, malodorous, yellow-green vaginal discharge with vulvar irritation. Some women may be asymptomatic.
TREATMENT
Desired Outcome
The desired outcome is the complete eradication of T. vaginalis in both partners and elimination of the signs and symptoms observed.
Pharmacologic Therapy
The 5-nitroimidazoles have been the standard therapy for trichomoniasis for over 40 years. Drugs included in this class are metronidazole, tinidazole, ornidazole, and secnidazole; metronidazole and tinidazole are the only drugs in this class available in the United States. When recommending the 5-nitroimidazoles, advise patients to avoid the consumption of alcohol.
Clinical Presentation of Trichomoniasis21
General
• Asymptomatic
Signs
• Strawberry cervix (women)
• Colpitis macularis (women)
• Prostatitis or epididymitis (men)
Symptoms
• Vaginal/vulvar erythema
• Excessive yellow-green discharge
• Vulvar itching
• Vaginal odor
• Urethral discharge or irritation
• Dysuria
• Vaginal pH greater than 4.5
Metronidazole
Metronidazole may be administered orally as a single 2-g dose or 500 mg twice daily for 7 days.22 Pregnant women should be prescribed the single dose of metronidazole. Cure rates are greater than 90% when metronidazole is administered as either a single 2-g dose or a 7-day regimen. Possible adverse effects include an unpleasant metallic taste, reversible neutropenia, urticaria, rash, flushing, dry mouth, darkened urine, and a disulfiram-like reaction.
Tinidazole
Tinidazole, a second-generation nitroimidazole with protozoal and anaerobic activity, has been available outside the United States for over 30 years.23 As a single 2-g dose, tinidazole has an efficacy equivalent to a 2-g dose of metronidazole. Tindazole also has a longer half-life than metronidazole, 14 and 7 hours respectively, and penetrates into male reproductive tissue better than metronidazole.
Tinidazole is effective for metronidazole-resistant trichomoniasis.24 Possible side effects include a metallic taste, dizziness, loss of coordination, seizures, severe diarrhea, darkened urine, nausea, vomiting, and a swollen or discolored tongue.
PATIENT CARE AND MONITORING
Monitoring for T. vaginalis is generally not required.
GENITAL WARTS
Genital warts, caused by the human papillomavirus (HPV), are regularly encountered in primary care. Responsible for various visible, keratotic, and nonkeratotic manifestations, HPV has nearly 120 noted strains, some of which have been linked to squamous cell carcinoma.25 More than 30 strains have been linked to the genital area.
EPIDEMIOLOGY
Affecting over 20 million Americans, HPV is one of the most common STIs in the United States, with a prevalence of approximately 15%. Furthermore, among adolescent and college-aged women, HPV may be the most common STI.4,20 The frequency of cervicovaginal HPV infection among sexually-active women has been observed at 43%, with the greatest incidence noticed in men with three or more sex partners and women whose most recent regular sexual partner had two or more lifetime partners.
PATHOPHYSIOLOGY
HPV replicates in terminally differentiated squamous cells in the intermediate layers of the genital mucosa. Hence, these effects of the viral early region genes on DNA synthesis are critical for viral survival. Genital warts are the clinical manifestation of active viral replication and virion production at the infection site.
DIAGNOSIS
• A definitive diagnosis of HPV is based on DNA or RNA or capsid protein detection.
• Diagnosis is generally made from the clinical presentation and may be classified into several categories: classic condyloma acuminata, which are pointed or cauliform; keratotic warts with a thick, horny surface resembling common skin warts; and flat warts, frequently observed on the surface.
Clinical Presentation of Genital Warts27,28
General
• Appear as rough, thick, cauliflower-like lesions
Signs
• Black dots within warts
• Disrupted surface
Symptoms
• Anogenital pruritus
• Burning
• Vaginal discharge or bleeding
• Although rare, dyspareunia may occur with vulvovaginal condyloma
• Tissue biopsy or viral typing is only indicated if diagnosis is uncertain and is not recommended for patients with routine or typical lesions.
• Since HPV is highly associated with cervical cancer and since there are more than 20 different cancer-associated HPV types, patients who are diagnosed with HPV should be tested for cervical cancer.
TREATMENT
Desired Outcome
Removal of visible warts and reduction of infectivity are the goals of treatment.
Pharmacologic Therapy4,26
Currently, the choice of therapy is based on the size, site, and morphology of lesions, as well as patient preference, treatment costs, convenience, adverse effects, and clinician experience. Factors that might affect response include the presence of immunosuppression and patient compliance. Assuming that the diagnosis is correct, switching to alternate therapy is appropriate if there has been no response observed after three treatment cycles. A comparison of adverse effects related to treatment options may be found in Table 80–2.
Table 80–2 Comparison of Adverse Effects Seen With Treatments for Genital Warts
Patient-Applied Treatment
Podofilox Available as a 0.5% gel or solution containing purified extract of the most active compound of podophyllin, podofilox arrests the formation of the mitotic spindle, prevents cell division, and may also induce damage in blood vessels within the warts. The surface area treated must not exceed 10 cm2, and a maximum of 0.5 mL should be used on a daily basis.
Apply twice daily for three consecutive days followed by four consecutive days without treatment. This cycle may be repeated until there are no visible warts or for a maximum of 4 weeks. Side effects are generally local and may include erythema, swelling, and erosions. Podofilox is not recommended for use in the vagina, anus, or during pregnancy.
Imiquimod Imiquimod is a cell-mediated immune-response modifier, available as a topical 5% cream in single-dose application packets. There are two recommended dosage regimens:
1. Apply at bedtime, three times a week for up to 16 weeks.
2. Apply every other day for three applications.
The treatment area should be washed with soap and water 6 to 10 hours after application. Mild to moderate erythema has been noted with imiquimod use; however, this generally suggests that the drug is reaching a therapeutic range and may be clearing the lesion.27
Physician-Applied Treatments
Podophyllin Resin28 A 10% to 25% solution of podophyllin resin has been the standard in-office treatment for genital warts. It is neurotoxic and due to its systemic absorption, a small amount (no more than 0.5 mL) should be applied. Application should be limited to less than 0.5 mL of podophyllin on an area of less than 10 cm2 of warts per session and no open lesions or wounds should exist in the area to which treatment is administered. The affected area will likely become erythematous and painful within 48 hours of application.
Topical podophyllin is applied once weekly and the area should be allowed to dry. Immediately following treatment, the dried drug should be removed using alcohol or soap and water. It is contraindicated in pregnant patients.
Bichloroacetic and Trichloroacetic Acids These products are available in 80% to 90% concentrations and are not systemically absorbed. The products are effective when used to treat a few, small, moist lesions. They may be applied to both keratinized epithelial and mucosal surfaces and may be used in pregnancy.
A noted reaction to these medications is transient burning, and contact with surrounding epithelium may prove to be painful, producing significant local erythema and swelling. To avoid these effects, place petroleum jelly around the external lesion, including unaffected skin, and carefully apply the agent with a small applicator. If an excess amount of acid is used, talc or sodium bicarbonate (baking soda) may be used to neutralize unreacted acid.
Other Treatments26 Other treatments may include fluorouracil/epinephrine/bovine collagen gel, an intralesional injection that has been proven effective in clinical trials for refractory patients, or an intralesional injection of interferon.
Ablative Therapy
Several ablative options have been employed in the treatment of genital warts and include cryotherapy, surgical removal, and vaporization.
Special Therapeutic Issues26,28
Large Warts Treat warts greater than 10 mm in diameter with surgical excision. Use imiquimod for three to four treatment cycles to reduce the number of warts and improve surgical outcomes. Fifty percent reduction in wart size after four treatment cycles warrants continued use of imiquimod until warts clear or eight cycles have been completed; less than 50% reduction warrants surgical excision or other ablative therapy.
Subclinical Warts Subclinical warts may be identified through colonoscopy, biopsy, acetic acid application, or laboratory serology. However, early treatment has not been linked to a favorable effect during the course of therapy in the index patient or the partner with regard to reduction of the transmission rate.
Pregnancy Agents contraindicated in pregnancy include podofilox, fluorouracil, and podophyllin. Imiquimod is not approved for use in pregnancy, although it has been considered after signed consent has been obtained. Bichloroacetic and trichloroacetic acids have been used without problems. Ablative therapy is also a viable option.
PATIENT CARE AND MONITORING
Monitor patients every 3 to 6 months for a reduction in lesions or disease remission. Monitoring parameters include patient compliance, disease remission, and benign or cancerous tumors.
GENITAL HERPES
Genital herpes, caused by herpes simplex virus (HSV) types 1 and 2, is a common STI for which there is no cure. Once latency is established, neither competent host immunity nor therapeutic agents can eradicate the virus. Currently, there is no vaccine available for HSV, and it seems that the development of one is unlikely in the near future.
EPIDEMIOLOGY
Despite a decline in the number of bacterial STIs, HSV-2 in adults has increased from approximately 20% to 32%.29 Prevalence of HSV-2 infection has grown by approximately 30% since the late 1970s, and currently over 500,000 new cases of HSV-2 occur annually.
Clinical Presentation of Genital Herpes30
General
• Asymptomatic
Classic Sign
• A cluster of painful vesicles on an erythematous base
Symptoms
• Itching
• Burning
• Tingling
• Groin lump
• Dysuria
• Dyspareunia
• Increased urinary frequency
Other Symptoms
• Ulcerative lesions, fissures, cervicitis
Patient Encounter 3
MR is a 19-year-old Caucasian female who visits a clinic complaining of intense itching and burning in the genital area for the past few days. She informed the clinician that she engaged in sexual intercourse within the past month and has also noticed an eruption of painful vesicles in the genital area. She is not sure of her partner’s sexual contacts.
What information is suggestive of genital herpes?
What potential risk factors for STIs are present?
What therapy should be recommended for this patient initially and how will this differ if episodic infection recurs?
PATHOPHYSIOLOGY
Since HSV is only found in humans, infection may only be transmitted from infectious secretions onto mucosal surfaces (i.e., cervix or urethra) or abraded skin. The virus may survive for a limited amount of time on environmental surfaces.
DIAGNOSIS
Laboratory confirmation is vital to effective treatment of HSV, especially in individuals in whom a clinical diagnosis cannot be obtained. There are several methods by which a definitive diagnosis may be acquired, and these include virologic typing, serologic diagnosis, rapid point-of-care antigen detection, enzyme-linked immunosorbent assay (ELISA), immunoblot, and DNA polymerase chain reaction.30Additionally, the FDA recently approved glycoprotein G-based assays to aid in the diagnosis of HSV.
TREATMENT
Desired Outcome
The desired outcome is to curtail the number of episodic prodromes and to minimize any side effects experienced due to the antivirals. Counseling of infected persons and their partners is vital to the management of HSV.
Pharmacologic Therapy
Treatment is based on several factors including likelihood of patient compliance, whether it is the first or a recurrent episode, host immunity, and pregnancy. However, patient response has been linked to the time it takes to initiate treatment after symptom onset.
First Episode
The first episode is a systemic illness associated with the vesicular lesions, may last up to 21 days, usually has an uncomplicated course of infection, and in severe cases may require hospitalization. Several agents are effective during this period (Table 80–3).31,32 At the cited dosages, these agents have had excellent outcomes with regard to lesion healing time, viral shedding, and loss of pain. Common adverse effects are nausea, headache, and diarrhea.
Episodic Therapy
In a patient with a previous diagnosis of genital herpes, the appearance of new vesicular lesions is synonymous with HSV reactivation. For most patients, genital herpes recurrence is self-limiting and shortlived, lasting approximately 6 to 7 days.
Suppressive Therapy
Suppressive therapy is effective for controlling all symptoms related to the disease and may impact troublesome complications of infection. Before beginning suppressive therapy, discuss patient expectations. Encourage patients to record any breakthrough episodes, as this may require treatment reevaluation and adjustment.
Preventive Therapy
Valacyclovir 500 mg orally once daily has been implicated to prevent the sexual transmission of HSV to an uninfected partner. In addition to pharmacologic therapy, counsel patients regarding safe sex practices.
Drug Resistance
Foscarnet, cidofovir, and trifuridine have been administered in acyclovir-resistant patients.33 These agents are usually reserved for use after other agents have failed because of their associated toxicities.
Pregnancy
Women who are pregnant may transmit the virus to the neonate during delivery. There are two management strategies: cesarean section and antiviral therapy. A few studies indicate that acyclovir 200 to 400 mg every 8 hours has been administered from 38 weeks gestation until delivery. The goal of therapy is to reduce the number of lesions and asymptomatic shedding at delivery.
Table 80–3 Comparison of Antivirals Used for Herpes Simplex Infection
Neonates
Herpes simplex virus infections should be considered in all neonates who present with nonspecific symptoms such as fever, poor feeding, lethargy, or seizures in the first month of life. Infants suspected to have or who are diagnosed with an HSV infection should be treated parenterally. Acyclovir 60 mg/kg/day in three divided doses IV for 14 days for disease limited to skin, eyes, and mucous membranes, and 21 days for CNS or disseminated disease is suggested.
PATIENT CARE AND MONITORING
Reevaluation of the patient’s condition and therapy adjustment are key elements in effective monitoring. Parameters may include:
• The patient’s psychosocial and psychosexual status
• Frequent reassessment of recurrent episodes and therapy adjustment
• Ordering tests for malignancy
• Yearly testing of HIV status
• Side effects of drugs
VACCINATIONS
Several HPV genotypes have been linked to the development of cervical cancer. HPV vaccine (Gardasil), developed to protect against HPV genotypes 6, 11, 16, and 18, is the first employed to prevent cervical cancer, precancerous genital lesions, and genital warts due to HPV. The CDC recommends the HPV vaccine for all 11- and 12- year-old females. Vaccination is also recommended for females aged 13 through 26 years who have not been previously vaccinated or who have not completed the full series of shots.34
The vaccine is given in a series of three injections over a 6-month period. The second and third doses should be given at 2 and 6 months (respectively) after the first dose. HPV vaccine may be given at the same time as other vaccines.
BACTERIAL VAGINOSIS
BV is a common infection and a recurrent cause of abnormal vaginal discharge in women of childbearing age. BV is categorized by an overgrowth of anaerobic organisms such as Gardenella vaginalis, Prevotella species, Mycoplasma hominis, and Mobiluncus species, leading to the replacement of lactobacillus and an increase in vaginal pH from 4.5 to 7.35 BV is the most prevalent cause of vaginal discharge and malodor.
EPIDEMIOLOGY
BV has been found in 12% to 25% of women in routine clinic populations, 10% to 26% of women in obstetrics clinics, and 32% to 64% of women in clinics for STIs. BV infection usually results from sexual activity, although some cases have been reported in women who are not sexually active.
PATHOPHYSIOLOGY
A complex and intricate balance of microorganisms maintains the normal vaginal flora (i.e., lactobacilli, corynebacteria, and yeast). The normal postmenarchal and premenopausal vaginal pH is 3.8 to 4.2. At this pH, growth of pathogenic organisms is usually inhibited; however, disturbance of the normal vaginal pH can alter the vaginal flora, leading to overgrowth of pathogens.
Clinical Presentation of Bacterial Vaginosis36
General
• Offensive fishy-smelling vaginal discharge
Signs
• Thin, white, homogenous discharge, coating the walls of the vagina
Symptoms
• Many women are asymptomatic; usually not associated with soreness, itching, or irritation
DIAGNOSIS
BV is diagnosed according to the Amsel criteria. In order for diagnosis to be confirmed, three of the four criteria must be present:
1. Thin, white, homogenous discharge
2. Clue cells on microscopy (clue cells are epithelial cells of the vagina that get their distinctive stippled appearance by being covered with bacteria)
3. pH of vaginal fluid greater than 4.5
4. Release of a fishy odor upon the addition of an alkali (10% potassium hydroxide) to a vaginal sample.
Alternatively, a gram-stain vaginal smear may be used to diagnose BV using the Nugent criteria. This relies on estimating the proportions of bacteria morphotypes to provide a score between 0 and 10. A score of less than 4 is normal, 4 to 6 is intermediate, and greater than 6 is consistent with BV. Isolation of G. vaginalis may not be diagnostic because it can be cultured from the vagina in some normal women, although a high concentration may be indicative of infection.36
TREATMENT
Desired Outcome
Reduction in the number of causative bacteria, cessation of vaginal discharge, and decrease in vaginal pH are the desired outcomes.
Pharmacologic Therapy4,37
Adults Recommended adult regimens include: Metronidazole 500 mg orally twice daily for 7 days or metronidazole gel (0.75%), one full applicator (5 g) intravaginally once daily for 5 days or clindamycin cream (2%), one full applicator (5 g) intravaginally at bedtime for 7 days.
Alternative regimens include: Clindamycin ovules 100 mg intravaginally once at bedtime for 3 days or clindamycin 300 mg orally twice daily for 7 days.
Pregnancy Pregnant symptomatic women should receive treatment. Treatment of BV in asymptomatic women at high-risk for preterm delivery with a recommended oral regimen mitigates preterm delivery. Screening should be performed during the first prenatal visit. Recommended regimens for pregnant women include: metronidazole 500 mg orally twice daily for 7 days or metronidazole 250 mg orally three times daily for 7 days or clindamycin 300 mg orally twice daily for 7 days.
PATIENT CARE AND MONITORING
A test to determine if the patient has been cured is generally not recommended. However, in patients with recurrent BV, a follow-up after the course of therapy may be warranted. If treatment has been prescribed during pregnancy to reduce preterm birth, perform a repeat exam in 1 month and advise further treatment for recurrent BV.
PELVIC INFLAMMATORY DISEASE
PID usually affects young, sexually-active, reproductive-age women. In the majority of cases, the pathogens responsible are C. trachomatis and N. gonorrhoeae; although anaerobes, enteric gram-negative rods, and cytomegalovirus have also been implicated in the pathogenesis.38 PID has been correlated with ectopic pregnancy, infertility, tubo-ovarian abscess, and chronic pelvic pain.
PATHOPHYSIOLOGY
Chlamydia may produce a heat-shock protein that causes tissue damage through a delayed hypersensitivity reaction. C. trachomatis may also possess DNA evidence of toxin-like genes that code for high-molecular-weight proteins with structures similar to Clostridium difficile cytotoxins, enabling inhibition of immune activation. This may explain the observation of a chronic C. trachomatis infection in subclinical PID.
DIAGNOSIS38,39
To be diagnosed with PID, patients must have uterine tenderness, cervical motion tenderness, and adnexal tenderness with no other cause of these signs. Additional criteria include:
• Oral temperature greater than 38.3°C (101°F)
• Abnormal cervical or vaginal discharge
• WBC presence on saline microscopy of vaginal secretions
• Elevated erythrocyte sedimentation rate
• Elevated C-reactive protein
Clinical Presentation of Pelvic Inflammatory Disease39
General
• Signs and symptoms may vary from mild to severe
Signs
• Vague
Symptoms
• Lower abdominal or pelvic pain
• Malodorous vaginal discharge
• Abnormal uterine bleeding
• Dyspareunia
• Dysuria
• Nausea and/or vomiting
• Fever
• Laboratory documentation of cervical infection with N. gonorrhoeae or C. trachomatis
TREATMENT
Desired Outcome
The removal of causative bacteria and reduction of any related sequelae are the desired goals of treatment.
Pharmacologic Treatment
Resolution of infection (i.e., N. gonorrhoeae, C. trachomatis, Streptococcus spp., and gram-negative facultative bacteria) and mitigation of sequelae should be the main goal of pharmacologic therapy. CDC-approved treatment regimens are shown in Table 80–4.4,38,43 Optimal management of PID should be individualized based on clinical setting and patient characteristics. For some patients, hospitalizations, IV antibiotics, and surgical treatment of complications may be needed. Though outpatient management remains contentious, many feel that outpatient management should be limited to individuals who: remain afebrile, have a WBC counts less than 11 × 103/mm3 (11 × 109L), have minimal evidence of peritonitis, have active bowel sounds, and can tolerate oral nourishment. Nonetheless, outpatient therapy with a parenteral cephalosporin or levofloxacin followed by doxycycline and metronidazole is recommended.
PATIENT CARE AND MONITORING
The goals of monitoring patients with PID are related to reducing long-term complications. To this end, the primary approach should be prevention and education of at-risk women. Secondary prevention may include screening by conducting a pelvic exam during a routine check-up.
Table 80–4 Treatment Regimens for PID
|
Parenteral |
|
Cefotetan 2 g IV every 12 hours or cefoxitin 2 g IV every 6 hours and doxycycline 100 mg orally or IV every 12 hours |
|
Oral |
|
Levofloxacin 500 mg orally daily for 14 days with or without metronidazole, 500 mg orally twice daily for 14 days |
• From Refs. 40–42.
CHANCROID
Haemophilus ducreyi, a gram-negative bacterium, has been isolated as the causative organism of chancroid, a genital ulcerative disease usually accompanied by inguinal lymphadenitis and bubo formation. Chancroid may possibly spread to other anatomic sites, a clinical feature first discovered by Ducrey in 1889.44
Clinical Presentation of Chancroid43
General
• The ulcer edge is commonly ragged and poorly defined.
Signs
• Four to seven days after infection, a tender, erythematous papule usually develops and subsequently progresses to the pustular stage.37 The pustules often rupture after 2 to 3 days.
• Lesions typically occur on the prepuce and frenulum in men and on the vulva, cervix, and perianal area in women. Some extragenital cases have been noted on the inner thighs, breasts, and fingers, though rarely seen in practice.
Symptoms
• Painful and tender lesions
• Painful shallow ulcers with granulomatous bases and purulent exudates.
EPIDEMIOLOGY
In 2003, more than 50,000 patients were diagnosed with chancroid in the United States. The majority of cases were diagnosed in the South Atlantic region, which included Delaware, North and South Carolina, Georgia, and Florida.45 Approximately 10% of persons who have chancroid that was acquired in the United States are coinfected with T. pallidum or HSV4; this percentage is higher in individuals who acquired chancroid outside of the United States.
PATHOPHYSIOLOGY
Transmission commences through direct contact with the skin, presumably through minor abrasions. The ulcer may be quite deep, and more than half of patients have multiple ulcers.
DIAGNOSIS
The multiplex polymerase chain reaction has been used successfully in diagnosis, demonstrating approximately 75% specificity in studies employing genital ulcer swabs. It offers an acceptable sensitivity in the detection of the three most common organisms involved in the etiology of genital ulcer disease: HSV, T. pallidum, and H. ducreyi.44,46 Additionally, several amplification techniques have been created in hopes of improving the sensitivity of laboratory diagnosis.
TREATMENT
Management of the syndrome has been the accepted approach of the WHO in lieu of the limitations seen with most diagnostic procedures. The prevailing thought is that patients should be treated during the first visit with a combination of antibiotics to cover for probable etiologic organisms.46
Table 80–5 Recommended Treatment Regimens for Chancroid from WHO and CDC
Desired Outcome
The desired outcome is to treat the ulceration, resolve the symptoms, and reduce the spread of infection to others.
Pharmacologic Therapy
The WHO- and CDC-recommended treatment regimens are shown in Table 80–5.4,44 There has been some debate about a suitable dosage of ciprofloxacin in the treatment of chancroid. Though the CDC recommends 500 mg orally three times daily, the WHO supports a single 500-mg oral dose. Ciprofloxacin has demonstrated an acceptable cure rate for a single dose (92%) when compared to erythromycin (91%). Ciprofloxacin is contraindicated for pregnant and lactating women.
PATIENT CARE AND MONITORING
Follow-up should include patient education, counseling, and repeated inspections of the ulceration to ensure healing. Examine patients 3 to 7 days after commencing with treatment. Ulcers usually improve symptomatically within 3 days and objectively within 7 days. If improvement is not evident, consider the following: (a) the diagnosis is incorrect; (b) the patient is coinfected with another STI; (c) the patient is infected with HIV; (d) the patient was noncompliant; or (e) the H. ducreyi strain may be resistant to therapy.
PREVENTION STRATEGIES
A combination of prevention efforts is advised. Alteration in sexual behavior should undoubtedly be the first counseling concern, as promiscuous sexual activity has been shown to augment the probability of infection.
Abstinence is the best course of action, especially in patients with herpes during lesional episodes. However, compliance in some may be minimal, in which case, appropriate condom use should always be recommended. To alleviate any possible misconceptions about condom application, either demonstrate how to apply a condom or ask the patient to demonstrate. During the demonstration, explicitly educate the patient with regard to application, storage, and the use of lubricants.47
Abbreviations Introduced in This Chapter
Self-assessment questions and answers are available at http://www.mhpharmacotherapy.com/pp.html.
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