Antibiotic Therapy for Epididymitis

US Pharm. 2015;40(8):39-43.

ABSTRACT: Epididymitis, an inflammation of the tube found posterior to the testicle, accounts for a significant number of physician office visits annually. Men diagnosed with epididymitis are typically between the ages of 18 and 35 years and present with a gradual onset of scrotal pain as well as symptoms mimicking urinary tract infection. While the condition is often a result of sexual activity, other risk factors may include prolonged sitting, bicycle or motorcycle riding, prostatic obstruction, and certain medications. Empirical antibiotic therapy should cover Chlamydia trachomatis, Neisseria gonorrhoeae, and Escherichia coli, the most common infecting pathogens. Pharmacists may provide consultation on appropriate antibiotic therapy and dosing.

Genitourinary issues account for a significant number of visits to outpatient primary care offices and emergency rooms each year. Of these conditions, epididymitis—inflammation of the epididymis (the tube posterior to the testicle that carries and stores sperm)—constitutes more than 600,000 diagnoses of men between the ages of 18 and 35 years annually in the United States.^1,2 Although no established measure has been documented, the socioeconomic impact of epididymitis is suggested to be substantial given that this condition often occurs during a man’s most productive years of life.³

Ongoing symptoms of or damage resulting from epididymitis, including infertility, can greatly impact a patient’s quality of life. In one survey, 84% of patients with chronic epididymal pain described their quality of life as “unsatisfying or terrible.”⁴ In order to help minimize the effects of epididymitis, it is necessary for practitioners to understand the various causes of this condition and the evidence-based treatments recommended.

Clinical Presentation

Epididymitis can occur alone or in conjunction with orchitis, inflammation of the testis. Epididymitis can be further classified as acute (symptoms for <6 weeks) or chronic (symptoms for >3 months).⁵ Patients with epididymitis usually present with gradual onset of unilateral scrotal pain, discomfort, and tenderness in addition to palpable swelling.² Fever, urgency, hematuria, dysuria, and other symptoms associated with lower urinary tract infections may also be present.¹

Symptoms of epididymitis can mimic other conditions such as malignancy or testicular torsion; thus, it is important to exclude other potential diagnoses.⁶ Testicular torsion is a medical emergency characterized by more severe pain with a sudden onset and should be referred to the emergency department.⁷

Etiology

Sexual activity is reported as the most common risk factor for epididymitis; however, those who are not sexually active may be at risk too. Participating in strenuous physical activity, riding a bicycle or motorcycle, or sitting for prolonged periods of time increase the chance for epididymitis.¹ In men aged >35 years and in prepubertal boys, recent urinary tract surgery or instrumentation and anatomical abnormalities (e.g., prostatic hypertrophy) are common causes.¹

Epididymitis may be caused by a virus or bacterium, but bacterial infection is the more common etiology.⁸ The most common pathogens associated with epididymitis are Chlamydia trachomatis, Neisseria gonorrhoeae, and Escherichia coli.⁴ C trachomatis and N gonorrhoeae are the most common causes of epididymitis in sexually active men aged <35 years.^9,10 Enteric organisms, such as E coli, are frequently the cause of epididymitis among men who have benign prostatic hyperplasia (BPH), urinary tract instrumentation, or surgery or who practice insertive anal sex.^2,4 Other less common organisms associated with epididymitis include Haemophilus influenzae, Ureaplasma urealyticum, Proteus mirabilis, Klebsiella pneumoniae, Enterococcus faecalis, and Pseudomonas aeruginosa.^1,8

Epididymitis is also linked to the granulomatous condition caused by Mycobacterium tuberculosis. It is thought, however, that spread of this bacterium occurs through the blood rather than through the urinary tract system.^2,4

Though bacterial pathogens are prevalent in a majority of epididymitis cases, noninfectious causes such as medical procedures, tumors, autoimmunity, and inflammation should not be overlooked.⁸ In children, viral infections (including enteroviruses and adenoviruses) and resulting postinflammatory reactions are thought to be a significant cause of epididymitis.^4,11 Additionally, medication-induced epididymitis has been reported with the use of amiodarone. Higher concentrations of amiodarone accumulate in the epididymis, causing antibodies to develop and attack the lining of the epididymis, which then produces inflammation.^12,13 Other noninfectious causes of epididymitis include trauma to the epididymis and Behçet disease, a multi-organ disorder that causes inflammation of the blood vessels.⁴ Some epididymitis cases remain idiopathic in nature. TABLE 1 summarizes possible etiologies.^4,11-13

Diagnosis

Patients presenting with symptoms consistent with epididymitis should undergo a thorough physical examination and laboratory testing to confirm the diagnosis and determine causative pathogens. Common laboratory tests include a CBC, urinalysis, urine culture, urethral culture, and Gram stain.^2,7 An accurate social and medical history should be obtained to determine patient risk factors for specific causative pathogens.² Sexually active men <35 years of age should be tested for C trachomatis and N gonorrhoeae by the nucleic acid amplification test (NAAT). Additional testing may be necessary for N gonorrhoeae if antibiotic resistance is a concern.¹⁴ If a fungal, mycobacterial, or enteric bacterial infection is suspected, a tissue aspirate or biopsy may be obtained for culture.¹⁴ Use of ultrasound in diagnosis should be limited to patients with scrotal pain who cannot be diagnosed by the methods previously discussed or when testicular torsion is suspected.²

Treatment

The goals of therapy for epididymitis include symptom relief, resolution of causative factors, and prevention of complications (TABLE 2).^2,4,5,13,15 Since bacterial pathogens cause the majority of cases, antibiotic therapy is the mainstay treatment of epididymitis. Some have criticized the current treatment guidelines for their emphasis on antibiotics; however, a recent study found that empirical antibiotic therapy for acute epididymitis is adequate based on studies published several years ago.^4,10 Treatment strategies beyond antibiotic therapy may be employed for patients who experience nonbacterial or chronic epididymitis. The main focus of treating these patients is symptomatic relief.^3,5

Symptomatic Relief

Symptomatic relief of epididymitis involves the use of nonpharmacologic and adjunctive therapies. Recommendations include bed rest, cold compresses, scrotal elevation, anti-inflammatory medications, and analgesics.^1,4,15

Acute Epididymitis

The mainstay of treatment is empirical antibiotic therapy (TABLE 3),² which is based on patient characteristics such as age and sexual history as well as most probable pathogens.⁴ If obtained, culture results can be used to select targeted antibiotic therapy. According to the CDC, if epididymitis is likely caused by C trachomatis or N gonorrhoeae, empirical antibiotic therapy that covers both pathogens should be initiated before laboratory results confirm the suspected pathogen. A single dose of ceftriaxone 250 mg IM should be given to eradicate N gonorrhoeae, and doxycycline 100 mg orally twice a day for 10 days should be given to eradicate C trachomatis.^2,16 Alternatively, a single dose of azithromycin 1 g orally may replace doxycycline to cover C trachomatis.¹⁷

Patients who are infected with a resistant strain of N gonorrhoeae or who have a severe cephalosporin allergy may be treated with gentamicin 240 mg IM plus azithromycin 2 g orally or gemifloxacin 320 mg orally plus azithromycin 2 g orally.¹⁸ If enteric organisms are the likely cause or if the NAAT determines that the infection is not caused by N gonorrhoeae, a fluoroquinolone antibiotic should be initiated.² Patients at risk of infection by sexually transmitted and enteric organisms should receive ceftriaxone and a fluoroquinolone.²

Nonbacterial Causes

Young boys who present with epididymitis resulting from an inflammatory condition following an infection may be given analgesics for symptomatic relief. These cases are typically benign and do not require antibiotic therapy.¹⁹ For patients who take amiodarone and no other cause of epididymitis can be found, amiodarone should be discontinued or the dose reduced to alleviate symptoms.^4,13

Chronic Epididymitis

No well-established therapy exists for the treatment of chronic epididymitis. Mild cases may warrant conservative therapy, which includes nonpharmacologic measures to minimize symptoms and watchful waiting.³ Common pharmacologic therapies include antibiotics, anti-inflammatory agents, anxiolytics, and narcotic analgesics.⁵

If pharmacologic and conservative therapies fail to relieve a patient’s chronic epididymitis, an epididymectomy may be considered as a last resort.¹⁵ Epididymectomy cure rates for chronic epididymitis are low, and patients should consider this when weighing the risks and benefits of undergoing the operation.²⁰

Follow-up

If a patient’s symptoms do not improve within 48 hours of initiation of therapy, he should return to his healthcare provider for further evaluation.² Most mild, acute cases of epididymitis do not warrant follow-up upon completion of therapy; however, persistent symptoms such as swelling and tenderness necessitate further evaluation for differential diagnoses or infection by uncommon pathogens.^2,7

Management of Sexual Partners

Sexual partners of the patient should be informed and evaluated for treatment if the cause of epididymitis is suspected or confirmed to be N gonorrhoeae or C trachomatis and sexual contact occurred within 60 days before symptom onset.² Treatment of sexual partners is important to decrease the transmission of infection and prevent complications associated with infection. Failure to treat sexual partners results in negative outcomes for the patient as well as any sexual partners. The patient may experience recurrence of infection and epididymitis, and the sexual partner may experience complications of infection. Common female complications of untreated infection include pelvic inflammatory disease, ectopic pregnancy, infertility, and chronic abdominal pain.^4,21 A serious complication of untreated infection in men, epididymo-orchitis, may result in infertility.^21,22

Patient-delivered partner therapy is the most common way that expedited partner therapy is executed. In this method, a physician provides a prescription for antibiotic treatment to the patient to give to his or her sexual partner.^16,23 Patient-delivered partner therapy should only be considered if it is appropriate for the individual case and legal within the state.^16,23

Complications

Complications associated with epididymitis can be serious. Acute epididymitis may progress to a more chronic epididymitis with ongoing pain and discomfort. Though somewhat rare, testicular abscesses, death of testicular tissue due to lack of blood flow (testicular infarction), and infertility are also possible complications.²⁴ Epididymitis may permanently damage the epididymis, resulting in infertility.⁸ The epithelium of the epididymis is not regenerative, which highlights the importance of effective treatment of epididymitis in reducing the inflammatory process to prevent damage.⁸

Conclusion

Epididymitis is a common urogenital condition prompting male patients to seek medical care because of scrotal pain and other uncomfortable symptoms. Whether acute or chronic, epididymitis has the potential to significantly impact quality of life. Since bacterial infections are the most common cause of epididymitis, empirical antibiotic therapy is the mainstay of treatment. Understanding the causes of epididymitis and appropriate treatment regimens can enable pharmacists to optimize patient outcomes and decrease the incidence of serious complications.

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