PROSTATITIS 

References:  JAMES J. STEVERMER, M.D., M.S.P.H., and SUSAN K. EASLEY, M.D. Treating Prostatitis. Am Fam Physician 2000;61:3015-22,3025-6.

Overview

Prostatitis is an inflammation of the prostate gland. The term prostatitis describes a wide spectrum of disorders ranging from acute bacterial infection to chronic pain syndromes. Prostatitis describes a wide number of maladies with variable etiologies, prognoses and treatments. Unfortunately, these conditions have not been well studied, and most recommendations for treatment are based primarily on case series and anecdotal experience. Prostatitis can be a challenging condition to treat. 

Etiology

Etiology depends on the classification of the prostatitis. Most of the cases of acute bacterial prostatitis are the result of gram-negative bacteria.

Around 87% of the cases of acute bacterial prostatitis (ABP) are due to E coli (most common cause). The following can also cause ABP Pseudomonas, Proteus, Klebsiella, and polymicrobial infections. Occasionally Streptococcus, Anaerobes, Ureaplasma, Mycoplasma genitalium, Trichomonas vaginalis, Chlamydia trachomatis, and Candida can cause ABP.  Enterococci account for 5% to 10% of documented acute infections.

The overwhelming majority of infections are due to Gram-negative rod shaped bacteria. Twenty percent of patients may have two or more different kinds of Gram-negative bacilli present in the prostate.

Neisseria gonorrhoeae should be suspected in sexually active men younger than 35 years. In patients with immune deficiencies (e.g., AIDS), pathogens like Mycobacterium tuberculosis, Serratia, and various fungi (i.e., Candida, Histoplasma, Aspergillus, and Cryptococcus) have been found.

In chronic bacterial prostatitis (CBP) the most common pathogens include E coli (over 80%), followed by Klebsiella, Pseudomonas, Proteus and Chlamydia. After E coli, gram-positive Enterococcus is the next most commonly isolated pathogen of CBP.

Manifestations

Acute Bacterial Prostatitis (ABP): Because acute infection of the prostate is often associated with infection in other parts of the urinary tract patients may also have symptoms consistent with cystitis or pyelonephritis. The diagnosis of acute bacterial prostatitis is often based on symptoms alone. Urinary symptoms can be irritative (i.e., urinary frequency, urgency, and dysuria) or obstructive (i.e., hesitancy, poor or interrupted stream, straining to void, and incomplete emptying). Pain may be present in the suprapubic or perineal region, or in the external genitalia. Systemic symptoms of fever, chills, malaise, nausea, emesis, and signs of sepsis (tachycardia and hypotension) may also be present. The patient may also experience decreased libido or impotence, or painful ejaculation.

When conducting a physical examination, the prostate should be gently palpated. A vigorous digital examination of the prostate should be avoided because it can induce bacteremia or cause the bacteremia, if present, to be worse. The prostate is usually tender, enlarged, and boggy. Abdominal examination may reveal a palpable, distended bladder demonstrating urinary retention.

Chronic Bacterial Prostatitis (CBP): CBP is a common cause of recurrent urinary tract infections in men. CBP is a persistent bacterial infection of the prostate lasting more than three months. Urine cultures obtained over the course of illness repeatedly grow the same bacterial strain. Unlike men with ABP, patients with CBP do not appear ill. They present with recurrent or relapsing urinary tract infections, urethritis, or epididymitis with the same bacterial strain. Between symptomatic episodes, detectable pathogens persist on localization tests. Patients may have irritative voiding symptoms and testicular, perineal, low back, and occasionally distal penile pain. On physical examination, patients are usually afebrile, and on digital rectal examination the prostate may feel normal, tender, or boggy.

Chronic Nonbacterial Prostatitis/Chronic Pelvic Pain Syndrome- Inflammatory and noninflammatory (CNP/CPPS): In men going to urologic referral centers more than 90% meet the criteria for CNP/CPPS. The hallmark symptom of CNP/CPPS is pain attributed to the prostate (e.g., painful ejaculation, pain in the penis, testicles, or scrotum, low back pain, rectal or perineal pain, or even pain along the inner aspects of the thighs) with no demonstrable evidence of infection. They oftentimes have irritative or obstructive urinary symptoms and decreased libido or impotence. They usually do not have recurrent urinary tract infections. On examination, tenderness of the prostate, or less commonly the pelvis, is present in about 50% of patients

Asymptomatic Inflammatory Prostatitis: It is defined at an incidental observation of leukocytes in prostatic secretions or tissue obtained during evaluation for other disorders, (e.g., leukocytes present in prostate biopsies obtained due to elevated PSA). Symptomatic prostatitis can elevate the PSA test to abnormal levels. Patients being evaluated for other prostatic diseases may have prostatitis on biopsy.

Epidemiology

• In the U.S. about 30% of men between 20 and 50 experience “prostatitis-like” symptoms with over 1 million physician office visits per year.

• Chronic and nonbacterial prostatitis are the most frequent diagnoses.

• Acute bacterial prostatitis is less common with an incidence of less than 1 in 1000 adult men per year.

• Prostatitis is the most common urologic diagnosis in men under 50 years of age and the third most common in men over 50.

• Patients with a previous episode of prostatitis were more likely to experience future episodes of prostatitis.

• 15% of men who visit a physician for genitourinary complaints are diagnosed with prostatitis.

• Acute bacterial prostatitis affects 2-5% of patients with prostatitis. Chronic bacterial prostatitis affects 2-5% of prostatitis patients. Chronic Nonbacterial Prostatitis/Chronic Pelvic Pain Syndrome affects 90-95% of patients with prostatitis.

• Asymptomatic inflammatory prostatitis is present in up to 32.2% of men with elevated PSA levels.

Pathogenesis

Acute bacterial prostatitis (ABP): The strains of E coli that cause ABP usually produce the following virulence factors: P fimbria, S fimbria, alpha-hemolysin, and cytotoxic necrotizing factor 1. Two main mechanisms for acute bacterial prostatitis have been proposed.

• Reflux of infected urine into the glandular prostatic tissue via the ejaculatory and prostatic ducts.

• Ascension of a urethral infection from the meatus, particularly during sexual intercourse.

Acute bacterial prostatitis: Inflammation of the prostate. Numerous PMN's in and around the acini, associated with intraductal desquamation, cellular debris and tissue invasion by lymphocytes, plasma cells, and macrophages. Microabscesses may occur and develop into large abscesses.

Chronic Bacterial Prostatitis (CBP): Research suggests that the E coli strains obtained from patients with CBP produce more virulence factors (P fimbria, S fimbria, alpha-hemolysin, and cytotoxic necrotizing factor 1) and are more likely to produce a biofilm than the strains obtained from patients with uncomplicated urinary tract infections. This may explain why CBP is difficult to treat.

Mechanisms involved in other chronic forms of prostatitis are just beginning to be proposed and appear to result from an interaction between physiological factors and dysfunction in the immune, neurological and endocrine systems.

Chronic forms of prostatitis: Less inflammation of the prostate. Plasma cells and macrophages infiltrate in and around the acini.

Diagnosis

Acute Prostatitis: The diagnosis of acute bacterial prostatitis is usually made based on symptoms alone. Midstream clean-catch urine culture should be obtained. The presence of > 10 white blood cells/hpf suggests a positive diagnosis. Other laboratory testing (e.g., CBC, electrolyte levels, blood culture) maybe needed if the patient illness is severe (e.g., fever, vomiting, hypotension). Post-micturation residual urine (i.e., insert a catheter post-micturation and drain the bladder completely) should be documented if a patient has a palpable bladder or symptoms consistent with incomplete emptying.

Chronic Bacterial Prostatitis: CBP is a persistent bacterial infection of the prostate lasting more than three months. Urine cultures obtained over the course of illness repeatedly grow the same bacterial strain. The diagnosis is based on history and physical examination, a voiding test such as the 2-glass pre- and post-prostatic massage test, and a positive urine culture.

Chronic Nonbacterial Prostatitis/Chronic Pelvic Pain Syndrome- Inflammatory and noninflammatory (CNP/CPPS): Evaluation and diagnosis of CNP/CPPS can be confusing and challenging for the treating physician. Many of the diagnostic tests performed in affected patients are geared toward excluding other treatable pathology (e.g., benign prostatic hyperplasia, bladder cancer), and urology referral is often necessary. Although its validity in diagnosing CNP/CPPS is in question the 2-glass pre- and post-prostatic massage test is suggested along with urinalysis and midstream clean-catch urine culture.

Asymptomatic Prostatitis: This type of prostatitis is diagnosed when inflammatory cells are identified on prostate biopsy or leukocytes are noted on semen analysis during urologic evaluation for other reasons. 

Prostatitis is not easily diagnosed or classified. Patients often present with varied and nonspecific symptoms. The physical examination is frequently not useful. If the history and physical suggest prostatitis the four-glass test (Stamey-Meares four glass localization method) or the 2 glass pre- and postmassage test (PPMT) may be used to aid in diagnosis.

In the Stamey-Mears tests patients are asked to urinate their first 10 ml of urine into a sterile cup (VB1; voided bladder 1). Then, they are asked to urinate from their midstream into a second sterile cup (VB2; voided bladder 2). Next, the prostate is massaged and expressed prostatic secretions are collected (EPS; expressed prostatic secretions). Finally, another 10 ml of urine is collected (VB3; voided bladder 3) to finish the "four glass collection." All four samples are sent to the lab and quantitative cultures are performed to get CFU/ml (>100,000 CFU/ml is positive) and centrifuged to count white blood cells/high powered field (>10/hpf is positive).

The 2 glass PPMT is more commonly used to diagnose prostatitis. Only VB2 and VB3 are collected and cultured. Both samples are sent to the lab and quantitative cultures are performed to get CFU/ml (>100,000 CFU/ml is positive) and centrifuged to count white blood cells/high powered field (>10/hpf is positive).

Even though the Stamey-Meares method is the gold standard it has not been assessed for its usefulness in the diagnosis or treatment of prostatitis. The expression of prostatic secretions required to perform this test can be difficult and uncomfortable. The test is cumbersome and expensive which may explain why many primary care physicians and urologists infrequently use it. In most cases, empiric antibiotic therapy is reasonable whether or not the diagnostic test proves a bacterial cause.

Prostate massage to express prostatic secretions should NOT be performed in patients with ABP because massaging the prostate can cause bacteremia.

Therapy

Acute Bacterial Prostatitis (ABP): Patients respond well to most antibiotics primarily because the prostate is inflamed. Antibiotics that are used include: trimethoprim-sulfamethoxazole or ciprofloxacin. Once the urine culture data has come back you can tailor treatment to the organism identified and to the antibiotics the organism is sensitive to. Men that are likely to get sexually transmitted diseases should be treated with an antibiotic that also covers Chlamydia sp. (i.e., doxycycline or azithromycin). Most experts recommend 6 weeks of antibiotic treatment.

If the patient is extremely ill (septic) they should be hospitalized and receive parenteral antibiotics. Treatment is similar to treatment for sepsis (e.g., ampicillin and gentamicin with ciprofloxacin or levofloxacin to be used in patients that are allergic to ampicillin or gentamicin) and should be given until the patient is afebrile. When afebrile they can be released from the hospital and given a 6-week prescription for oral trimethoprim-sulfamethoxazole, or ciprofloxacin. If the patient is still febrile after 36 h on parenteral antibiotics prostatic abscess should be suspected and a urology consult obtained. The urologist will usually order imaging of the prostate (e.g., computed tomography, magnetic resonance imaging, or transrectal ultrasonography). If negative by imaging for abscess, then the antibiotic used may need to be changed based on urine culture and sensitivity results. If positive for abscess the urologist will need to drain the prostatic abscess.

Chronic Bacterial Prostatitis (CBP): Fluoroquinolones (e.g., ciprofloxacin, levofloxacin, and norfloxacin) are able to get into the prostate at effective antimicrobial concentrations and are recommended as first-line agents. Second-line drugs include doxycycline, azithromycin, and clarithromycin. A four- to six-week course of therapy is usually recommended; however, a six- to 12-week course is often needed to eradicate the causative organism and to prevent recurrence, especially if symptoms persist after completion of the initial therapy.

Chronic Nonbacterial Prostatitis/Chronic Pelvic Pain Syndrome- Inflammatory and noninflammatory (CNP/CPPS): Treatment is challenging and very difficult. Failures are commonplace (66%). The following have success in some patients.

Asymptomatic Inflammatory Prostatitis: No treatment is recommended.

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