The usual approach to sexually transmitted diseases (STDs) considers the causative agents, emphasizing different classes, genera, species, and microbiological characteristics. This fits with most medical school curricula since the causative agents span the full spectrum of medical microbiology (viruses, bacteria, protozoa, ectoparasites, and so on). This classical approach often proves difficult in clinical practice, where many different types of agents must be considered in the differential diagnosis of an individual patient.

This chapter takes a very selective and practical approach. Because patients present with symptoms and signs that may be caused by pathogens from different microbiological classes, we will emphasize diagnosis and treatment of clinical syndromes in contrast to traditional teaching (Table 16–1). This is a large subject with much active research and a huge literature. We stress the most important conditions encountered in urology: urethritis, epididymitis, genital ulcers, genital warts, plus a brief consideration of human immunodeficiency virus (HIV) infection.

Urethritis in Men

Definition. Urethritis, or urethral inflammation, is frequently caused by infection.

Clinical presentation. Characteristically, patients complain of urethral discharge and dysuria. On examination, the discharge may be purulent or mucopurulent. Asymptomatic infections are common (CDCP, 2006; McCormack and Rein, 2000). The most important pathogens are bacteria, Neisseria gonorrhoeae, and Chlamydia trachomatis.

Laboratory testing. Testing is recommended to document a specific disease because both of these infections are reportable to health departments, and because specific diagnosis may improve compliance and partner notification (CDCP, 2006). The traditional diagnostic algorithm includes microscopic examination of the Gram-stained urethral smear for gram-negative intracellular diplococci and culture for N. gonorrhoeae. New nucleic acid amplification tests have proved accurate for detection of N. gonorrhoeae and C. trachomatis in first-void urine in high-risk populations (CDCP, 2006; Gaydos et al, 2009; McCormack and Rein, 2000). If diagnostic testing is unavailable, patients should be treated empirically for both infections (CDCP, 2006).

Complications. Complications of urethritis in men include epididymitis (see later), disseminated gonococcal infection, and Reiter’s syndrome (CDCP, 2006; McCormack and Rein, 2000). Complications of urethritis in female sexual partners include pelvic inflammatory disease, ectopic pregnancy, and infertility (CDCP, 2006; Mead, 2000). Complications in children include neonatal pneumonia and ophthalmia neonatorum (CDCP, 2006).

Etiology

Gonococcal and chlamydial infections. Gonorrhea is diagnosed when N. gonorrhoeae is detected by Gram stain, culture, or nucleic acid amplification testing. Nongonococcal urethritis (NGU) is diagnosed when gram-negative intracellular organisms cannot be diagnosed on microscopic examination or by diagnostic testing. C. trachomatis, the most common infectious cause of NGU, is responsible for 23–55% of cases in reported series, but the proportion of cases is substantially lower in urological practice. The prevalence of chlamydial infection differs by age group, with a lower prevalence among older men. In addition, the proportion of NGU caused by C. trachomatis has been declining. Documentation of chlamydial NGU is important because this diagnosis supports partner referral, evaluation, and treatment (CDCP, 2006; Krieger, 2000; McCormack and Rein, 2000).

Other infectious causes. The etiology of most cases of nonchlamydial NGU is unknown. The genital mycoplasmas, Mycoplasma genitalium, Ureaplasma urealyticum, and possibly Mycoplasma hominis, are implicated in 20–30% of cases in some series (Bradshaw et al, 2006; Gaydos et al, 2009; Ross et al, 2009; Stamm et al, 2007). Specific diagnostic tests for these organisms are not indicated routinely. Trichomonas vaginalis, a protozoan parasite, and herpes simplex virus (HSV) may also cause NGU (Gaydos et al, 2009; Hobbs et al, 2006; Martin, 2008). Testing and treatment for these organisms should be considered in situations where NGU is unresponsive to treatment (CDCP, 2006; McCormack and Rein, 2000; Shahmanesh et al, 2009).

Document Urethritis

It is important to document the presence of urethritis because some patients have symptoms in the absence of inflammation. Urethritis may be documented by the presence of any of the following clinical signs: mucopurulent urethral discharge on physical examination, ≥5 leukocytes per oil immersion microscopic field of the Gram-stained urethral secretions, a positive leukocyte esterase test on first-void urine, or ≥10 leukocytes per high-power microscopic field of the first-void urine (CDCP, 2006; McCormack and Rein, 2000). The Gram stain is the preferred diagnostic test for documenting urethritis and for evaluating the presence or absence of gonococcal infection because it is rapid, highly sensitive, and specific.

If none of the criteria for urethritis are met, then treatment should be deferred. The patient should be tested for both N. gonorrhoeae and C. trachomatis and followed up closely in the event of a positive test result.

Empiric treatment of symptoms without documenting the presence of urethritis is recommended only if the patient is at high risk for infection and is unlikely to return for follow-up. Empiric treatment should be appropriate for both gonococcal and chlamydial infection. Sex partners should be referred for appropriate evaluation and treatment.

Treatment of Gonococcal Infections

Epidemiology. There are an estimated 600,000 new gonococcal infections per year in the United States. In men, most infections cause symptoms that cause the patient to seek treatment soon enough to prevent serious sequelae. However, this may not be soon enough to prevent transmission of infection to sex partners. In contrast, many gonococcal (and also chlamydial) infections in women do not cause recognizable symptoms until the patient presents with complications, such as pelvic inflammatory disease (Mead, 2000). Symptomatic and asymptomatic pelvic inflammatory disease both result in tubal scarring, increased rates of ectopic pregnancy, and infertility.

Dual therapy for gonococcal and chlamydial infections. Dual therapy is recommended for both gonococcal and chlamydial infection because patients are often coinfected with both pathogens (CDCP, 2006; CDCP, 2007; McCormack and Rein, 2000). Quinolone-resistant N. gonorrhoeae have been reported from many geographic areas, and such infections are becoming widespread in parts of Asia (Ghanem et al, 2005; Perez-Losada et al, 2007; Rahman et al, 2002).

Antimicrobial resistance. Increasing antimicrobial resistance resulted in substantial changes in the gonorrhea treatment guidelines (CDCP, 2007). Fluoroquinolones (ie, ciprofloxacin, ofloxacin, or levofloxacin) were the most frequently used drugs for treating gonorrhea because of their high efficacy, ready availability, and convenience as a single-dose, oral therapy. Unfortunately, this practice resulted in increasing fluoroquinolone resistance in N. gonorrhoeae. Since 2000, quinolones could no longer be recommended for treating patients who acquired their infections in Asia, the Pacific Islands, or Hawaii. Progressive increases in resistance led to extension of these recommendations to patients in California in 2002, and to treatment of gonorrhea in men who have sex with men elsewhere in the United States in 2004. Recent increases in the prevalence of fluoroquinolone-resistant N. gonorrhoeae throughout the United States led to the conclusion that fluoroquinolones can no longer be recommended for treating gonococcal infections anywhere in the United States. Consequently, only one class of drugs, the cephalosporins, is still recommended and available for the treatment of gonorrhea (CDCP, 2007). Of the recommended cephalosporins, only cefixime is available in an oral formulation. Spectinomycin 2 g in a single dose is considered an effective alternative regime. But this drug is also not available in the United States. This means that there is only one available oral treatment recommended for gonorrhea in the United States.

Recommended regimens. Table 16–2 summarizes recommended treatment regimens for uncomplicated gonococcal infections, where the recommended treatments reliably cure ≥97% of infections (CDCP, 2006; CDCP, 2007). Pharyngeal infections are more difficult to treat, and few regimens reliably cure >90% of infections. Patients who cannot tolerate cephalosporins should be treated with spectinomycin (2 g as a single intramuscular dose). However, this regimen is only 52% effective for pharyngeal infections.

Routine test-of-cure cultures are no longer recommended for patients treated with the recommended regimens. Such patients should refer their sex partners for evaluation and treatment. However, patients should be reevaluated if their symptoms persistent after therapy. Any gonococci that persist should be evaluated for antimicrobial susceptibility. Infections identified after treatment are usually reinfections rather than treatment failures. Persistent inflammation may be caused by C. trachomatis or other organisms.

Complications. A few patients have complications such as disseminated gonococcal infection, perihepatitis, meningitis, or endocarditis. These infections result from gonococcal bacteremia. Disseminated gonococcal infection often causes petechial or pustular skin lesions, asymmetrical arthralgias, tenosynovitis, or septic arthritis. Occasionally, patients have perihepatitis, and rare patients have endocarditis or meningitis. N. gonorrhoeae strains that cause disseminated infection tend to cause minimal genital tract inflammation. The recommended treatment is ceftriaxone (1 g intramuscularly or intravenously every 24 hours for disseminated infection or 1 g intravenously every 12 hours for meningitis or endocarditis).

Treatment of Nongonococcal Urethritis

Treatment should be initiated as soon as possible after diagnosis (Table 16–2). Single-dose regimens are preferred because these treatments offer the advantages of improved compliance and directly observed therapy (CDCP, 2006). The recommended treatments employ either azithromycin or doxycycline. Alternative choices for patients who are allergic or cannot tolerate these drugs include a 7-day course of either erythromycin or ofloxacin. Routine follow-up and repeat testing are no longer recommended for patients taking the recommended regimens. However, patients should return for reevaluation if symptoms persist or recur after completion of treatment. The presence of symptoms alone without documentation of signs or laboratory findings of inflammation is not sufficient for retreatment. Patients should refer their sex partners for appropriate evaluation and treatment.

Treatment of Recurrent and Persistent Urethritis

Objective signs of urethritis should be documented before prescribing a repeat course of empirical therapy (CDCP, 2006; McCormack and Rein, 2000). Men with persistent or recurrent urethritis should be retreated with the initial regimen if they did not comply with treatment or if they were reexposed to an untreated sex partner. Other patients should have a wet mount and urethral culture for T. vaginalis. For patients who were compliant with the initial regimen and who were not reexposed, the regimen in Table 16–2 should be used. This provides treatment for both T. vaginalis and the genital mycoplasmas.

Mucopurulent Cervicitis in Women

Clinical findings. Mucopurulent cervicitis holds many parallels to urethritis in men (CDCP, 2006; McCormack and Rein, 2000; Mead, 2000). Characteristically, patients have a purulent or mucopurulent endocervical exudate visible in the endocervical canal or on an endocervical swab sample. Easily induced endocervical bleeding is also common, as is an increased number of polymorphonuclear cells on the Gram-stained endocervical secretions. Patients may present with abnormal vaginal discharge or abnormal vaginal bleeding, for example, after intercourse, but many are asymptomatic.

Diagnosis and treatment. As is the case with urethritis in men, N. gonorrhoeae and C. trachomatis are the most important infectious causes of mucopurulent cervicitis. However, neither pathogen may be identified in many women. Treatment should be guided by the results of testing for gonococcal and chlamydial infection, unless the patient is considered unlikely to return for follow-up. In such cases, empirical therapy should be given for both C. trachomatis and N. gonorrhoeae.

Definition and classification. Epididymitis is a clinical syndrome characterized by pain, swelling, and epididymal inflammation. Arbitrarily, epididymitis syndromes have been classified as acute, if symptoms have been present for less than 6 weeks, or chronic if symptoms have been present for 3 months or longer. Some experts suggest that chronic epididymitis may be subcategorized by etiology into inflammatory chronic epididymitis, obstructive chronic epididymitis, and chronic epididymalgia (Nickel et al, 2002).

Etiology. Epididymitis is caused by sexually transmitted pathogens or by organisms causing urinary tract infection (CDCP, 2006; Krieger, 2000). Among sexually active men younger than 35 years, most cases of epididymitis are caused by sexually transmitted pathogens, particularly C. trachomatis and N. gonorrhoeae. Epididymitis may also be caused by Escherichia coli among men who are the insertive partners during anal intercourse. Sexually transmitted epididymitis is usually associated with urethritis, which is often asymptomatic. Patients with uncomplicated sexually transmitted epididymitis do not require thorough evaluation for anatomic abnormalities.

Most cases of epididymitis in men older than 35 years are associated with urinary tract infection. The most common pathogens are gram-negative enteric bacteria. Epididymitis associated with urinary infection is more common among men who have anatomic abnormalities or those who have recently had urinary tract instrumentation. Therefore, evaluation of genitourinary tract anatomy is indicated for men with epididymitis associated with urinary tract infection.

Clinical presentation and diagnosis. Epididymitis is typically associated with unilateral hemiscrotal pain and tenderness. An inflammatory hydrocele and palpable swelling of the epididymis are characteristic. Diagnostic recommendations include a Gram-stained smear for evaluation of urethritis and for presumptive identification of gonococcal infection, diagnostic testing for N. gonorrhoeae and C. trachomatis, urine Gram stain and culture, syphilis serology, and HIV testing (if sexually transmitted epididymitis is likely).

Treatment. Outpatient management is appropriate for most patients with epididymitis. Hospitalization should be considered when severe pain suggests other possible diagnoses, such as testicular torsion, testicular infarction, or testicular abscess; when patients are febrile; or when noncompliance with medication regimens is likely (CDCP, 2006; Krieger, 2000). Empiric antimicrobial regimens are summarized in Table 16–3. Adjunctive measures include bed rest, scrotal elevation, and analgesics until fever and local inflammation subside.

Routine follow-up is recommended. Failure to respond within 3 days requires reevaluation of both the diagnosis and treatment. Swelling and tenderness that persist after completion of antimicrobial therapy should be reevaluated to consider other possible diagnoses. These conditions include testicular tumor, abscess, infarction, tuberculosis, fungal epididymitis, or collagen-vascular disorders (Cho et al, 2003; de Vries et al, 2001; Giannopoulos et al, 2001

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