Chronic Bacterial Prostatitis

Practice Essentials

Chronic bacterial prostatitis (CBP) is most often caused by Escherichia coli or other gram-negative Enterobacteriaceae, and typically affects men 36 to 50 years of age. After an episode of acute bacterial prostatitis, approximately 5% of patients may progress to CBP.^[1] Patients may present with a history of relapsing urinary tract infections (UTIs), which may be episodic or persistent. The UTIs are typically not associated with systemic signs of infection. Other irritative or obstructive urologic symptoms may also be present. (See Presentation).

Analysis of urine specimens and prostatic fluid is used to confirm the diagnosis (see Workup). The main diagnostic criterion for CBP is positive bacterial cultures of prostatic fluid. There is also often leukocytosis in prostatic fluid, which represents prostatic inflammation but is not specific to CBP.

For localization of UTI, the four-glass test is still considered the diagnostic standard, but it is cumbersome and has little use in the clinical setting.^[2] The two-glass test, also known as pre-massage and post-massage test (originally suggested by Weidner and Ebner in 1985 and supported by Nickel^{[3, 4]} ) is more commonly used, as it is simple and cost-effective.

However, some patients may have bacterial infection despite negative urine cultures. Negative culture results occur for various reasons, including insufficient sample volume, initiation of antibiotics prior to obtaining an EPS sample, and the presence of fastidious organisms. In such cases, patients often have symptom improvement after antibiotic treatment.

The most effective antibiotics for CBP are fluoroquinolones. Duration of treatment is typically 4 to 6 weeks. Best results have been observed with a 12-week course of therapy, but patient compliance may be difficult with such longer courses. Nonsteroidal anti-inflammatory drugs (NSAIDs) and alpha blockers help with symptom relief. Alpha blockers may also help to decrease recurrences, by diminishing urinary obstruction. See Treatment and Medication.

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Background

Prostatitis has been challenging to classify and diagnose. The "traditional" classification of prostatitis was based on 10 years of clinical experience with the "four-glass test" as landmarked by Meares and Stamey in 1968.^[5] The traditional classification described four prostatitis categories^[6] :

• Acute bacterial prostatitis (leukocytosis in prostatic fluid, positive bacterial cultures, systemic signs of infection)
• Chronic bacterial prostatitis (leukocytosis in prostatic fluid, positive bacterial cultures, no systemic signs of infection)
• Nonbacterial prostatitis (leukocytosis in prostatic fluid but negative cultures)
• Prostatodynia (pain and voiding symptoms, no leukocytosis in prostatic fluid, and negative cultures)

The National Institutes of Health (NIH) classification was developed in 1998 and replaced the traditional classification. This system has been generally accepted as the best for clinical research and practice.^[7] The NIH classification has the following four categories:

• Category I - Acute bacterial prostatitis
• Category II - Chronic bacterial prostatitis (CBP)
• Category III - Chronic pelvic pain syndrome (CPPS)
• Category IV - Asymptomatic inflammatory prostatitis

Category I is identical to the traditional classification system. Category II, the focus of this article, also has the same definition as the traditional classification system; it refers to patients with recurrent urinary tract infections (UTIs) suggesting a prostate nidus of infection.^[8]

Category III acknowledges that pain is the main symptom in prostatitis without uropathogenic bacteria. Category III, CPPS, is now the most commonly diagnosed type of prostatitis. It is subdivided into category IIIA, inflammatory CPPS, which is identical to non-bacterial prostatitis; and category IIIB, non-inflammatory CPPS, which is identical to prostodynia.

Category IV comprises case in which the patient has no symptoms, but leukocytosis or bacteria is found in prostate specimens. This diagnosis is often based on results of biopsies, surgical specimens, or semen analysis obtained for other reasons. No treatment is warranted.

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Anatomy and Physiology

The normal prostate gland weighs approximately 20 g and measures 3 cm in length, 4 cm wide, and 2 cm in depth. The prostate enlarges with aging in most men (ie, benign prostatic hyperplasia). The prostate is located in the pelvis and is in continuity with the base of the bladder superiorly and the striated external urethral spincter inferiorly. It is posterior to the symphysis pubis and anterior to the rectum. The prostate is innervated by sympathetic nerves from T-10 to L-1.

Although the prostate functions as a single glandular structure, it is divided anatomically into the following three distinct zones:

• The transitional zone surrounds the prostatic urethra proximal to the seminal colliculus (verumontanum), where ejaculatory ducts empty into the urethra.
• The central zone encases the ejaculatory ducts and runs toward the base of the bladder.
• The peripheral zone extends anterolaterally proximal to the verumontanum and then makes up the bulk of the gland distal to the verumontanum. A fibromuscular stroma exists anterior to the gland, running from the bladder neck to the striated sphincter. 

In the posterior midline of the prostatic urethra there is a groove called the urethral crest, surrounded by bilateral vertical ridges that are the urethral sinuses where prostatic glands drain. The verumontanum is a widened protrusion of the urethral crest, where the ejaculatory ducts drain bilaterally.

The prostate is 70% glandular tissue and 30% fibromuscular stroma. The glandular elements of the prostate are relatively simple tubuloalveolar glands that are lined with simple cuboidal or columnar epithelium. There are approximately 20 of these glands, and they branch out into the fibromuscular stroma and have single ducts that empty into the prostatic urethra at the urethral sinuses.

The prostate gland is an endocrine gland, providing approximately 15% of the ejaculate.

Natural host defenses that prevent prostatitis include the flushing of the prostatic urethra by emptying the bladder, ejaculation, and the presence of a zinc-rich antibacterial polypeptide that has antibacterial effects against gram-positive and gram-negative bacteria. The prostate has the highest level of zinc concentration of any organ. Healthy men have very high zinc levels, whereas men with chronic bacterial prostatitis (CBP) have low prostatic zinc levels and normal serum zinc levels. Interestingly, oral zinc supplementation does not increase the prostatic zinc levels in men with CBP.

Spermine and spermidine are also natural host defenses in prostatic fluid. These impart the characteristic odor to ejaculate, and their antibacterial activity is directed mainly at gram-positive bacteria.

For more information, see Prostate Anatomy

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Etiology

The recurrent UTIs in chronic bacterial prostatitis are secondary to uropathogens residing within the gland.

The gram-negative Enterobacteriaceae family of bacteria are the most common causative organisms, with Escherichia coli the most common strain, found in around 80% of cases.^{[9, 10]} Other bacteria of the Enterobacteriaceae family (ie, Pseudomonas aeruginosa, Serratia species, Klebsiella species, Proteus species, and Enterobacter aerogenes) make up another 10%-15% of infections. Enterococci are present in 5%-10% of prostate infections, but other gram-positive organisms have a questionable role as their localization in cultures in inconsistent.^[11]

The gram-positive organisms that typically colonize the anterior urethra (ie, Staphylococcus epidermitis, S saprophyticus, Streptococcus, Corynebacterium, and Bacteroides) may represent contamination when present in a culture specimen, and their role in prostatic inflammation remains unclear. Patients with these bacteria, even when localized to prostate specimens, are currently considered to have CPPS, but this may change as understanding of prostatic bacterial pathogenicity evolves.^[1]

Although Chlamydia trachomatis has been implicated as a cause of the condition,^[12]  the evidence is conflicting and unclear. Some studies have been able to isolate Chlamyida in specimens while other studies were unable to confirm Chlamydia as an etiologic agent using cultures and serologic tests. Treatment of presumed chlamydial prostate infections does not relieve symptoms in many cases and no definitive statement can be made about its prostatic origin and effect at this time.^[1]

Uropathogens

See the list below:

• E coli
• Klebsiella pneumoniae
• Pseudomonas aeruginosa    
• Proteus species
• Enterococcus species
• Trichomonas species
• Chlamydia trachomatis
• Ureaplasma urealyticum
• Mycoplasma hominis

Other microorganisms

Candida and other mycotic infections have been identified in cases of prostatic inflammation, but mostly in patients who have systemic fungal infections or are immunosuppressed. Viruses have also been implicated, but their role in prostatitis has not been formally evaluated.^[1] With limitations to culture techniques, some microorganisms may fail to be identified.

Bacterial virulence

Bacterial P-fimbriae facilitate colonization of the lower urinary tract by binding to urothelial receptors. E coli has mannose-sensitive fimbria with receptors that has been associated with the development of cystitis and prostatitis. 

Biofilm formation by bacteria allows the bacteria to persist despite antibiotic treatment. Biofilms are protective aggregates of bacteria that form in response to host defenses or antibiotic therapy; in prostatitis, they develop deep in the ducts of the prostate.^[13] Patients with organisms persisting in biofilms or within obstructed ducts may have persistent symptoms despite sterile cultures. Hemolysin may also increase the ability of bacteria to persist as biofilms, as seen with certain strains of E coli causing CBP.^[1]

Even after bacteria have been eradicated, the virulence of the specific bacteria may influence the development of CPPS.^[1]

Risk factors

Risk factors for CBP include the following:

• Intraprostatic ductal reflux and prostatic calculi
• Other infections (eg, acute epididymitis, urinary tract infections)
• Phimosis 
• Unprotected penetrative anal intercourse
• Manipulation of the lower urinary tract
• Secretory dysfunction of prostate gland 

Intraprostatic ductal reflux and prostatic calculi 

• The peripheral zone of the prostate is composed of a system of ducts with a poor drainage system, which prevents the dependent drainage of secretions and makes that zone the most susceptible to reflux. As the prostate enlarges with age, the poorly draining ducts can become obstructed and reflux.^[14]
• High-pressure dysfunctional voiding from anatomic or neurophysiologic obstruction may result in reflux in addition to contributing to symptoms of prostatitis with development of chronic pain.
• Pathogenic bacteria can directly enter the prostate via ascending urethral infection with refluxing urine and may exist as aggregates protected by prostatic calculi. 
• Refluxing urine, even when sterile, may cause chemical irritation and initiate tubule fibrosis and prostatic stone formation, which then can lead to intraductal obstruction and stagnation of intraductal secretions. Prostatic stones and stagnant fluid can serve as a nidus for relapsing infections and prostatitis.
• Prostatic calculi are generally evidence of intraprostatic reflux because they are composed of substances only found in urine and not in secretions from the prostate. They serve as a source of bacterial colonization allowing bacterial to aggregate or form biofilms leading to recurrent UTIs despite adequate antimicrobial therapy. 
• Prostatic calculi are also common in men with chronic inflammatory prostatitis, compared with men without prostate inflammation.^[15]

Manipulation of the lower urinary tract 

Treatments that increase risk include the following:

• Indwelling urethral catheters or condom catheters
• Transurethral surgery, especially in men with infected urine who have not been treated. 
• Prostate biopsy can irritate the prostate or cause an infection. Infections following prostate biopsy often involve organisms with different virulence and resistance than those from spontaneous acute infections of the prostate. Extended-spectrum β-lactamase (ESBL) E coli infection after prostate biopsy is a risk factor for chronic prostatitis.^[16]

Secretory dysfunction of prostate gland 

• Altered secretions can reduce the natural antibacterial nature of prostatic secretions. Findings in prostatic secretions during infections include a decrease in fructose, citric acid, acid phosphatase, zinc, magnesium, calcium, and prostatic antibacterial factor, as well as an increase in ceruloplasmin and complement C3. 
• It is unclear whether the changes in prostatic fluid are a cause or consequence of inflammation, but they correlate with inflammation and are blamed for reducing the antibacterial nature of prostatic secretions.
• Alkaline pH (up to 8.0) of prostatic fluid is associated with inflammation and can also reduce its antibacterial properties, as well as limit diffusion of some basic antimicrobials into the prostate. 
• Prostatic fluid is generally acidic, with a pH of 6.4 (compared with plasma pH of 7.4), thus creating a pH gradient that further inhibits diffusion of acidic antibiotics into the prostatic fluid. Basic antibiotics are able to dissociate and concentrate in the prostatic fluid because of ion trapping within the prostatic fluid due to the pH gradient. Therefore, the best antibiotics for use in prostatitis have high dissociation constants (ie, measure of acid strength), are basic instead of acidic, and are not tightly protein bound. This combination can allow up to a six-fold higher concentration of antibiotic in the prostatic fluid compared with plasma.
• Infection often persists because antibiotics do not easily penetrate the prostate and no active transport mechanism exists whereby antibiotics can enter the prostatic ducts. Therefore, antibiotics depend on passive diffusion to enter the epithelial-lined prostatic glandular acini. The epithelial cells do not allow the free passage of antibiotics unless they meet certain criteria (ie, non-ionized, lipid-soluble, not firmly protein bound).

Routes of infection

The actual routes of prostatic infection are unknown in most cases, but various possibilities exist. Ascending urethral infection is a known route because of the frequency of previous gonococcal prostatitis, as well as the finding of identical organisms in prostatic fluid and vaginal culture in many couples. Intraprostatic urinary reflux has been demonstrated in human cadavers and may play a role. Other possible routes of infection include hematogenous spread, migration of rectal bacteria via direct extension, and lymphogenous spread.

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Epidemiology

The lack of clear and strong epidemiological data for prostatitis likely reflects the previous lack of uniform definitions for the disorder and symptom overlap with other urological conditions. 

The prostatitis symptom complex is very common and is estimated to account for approximately 25% of urologic evaluations in men in the United States. Prostatitis accounts for approximately 2 million urology visits annually, or approximately 6% to 8% of all urology visits. Worldwide, about 8 million prostatitis-related outpatient visits occur annually.^{[1, 17]}

Studies using the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) found that the prevalence of prostatitis symptoms was 10% in a population of men aged 20-74 years. Overall, the prevalence of symptoms of prostatitis ranges from 2.2% to 16%, with a median of 7% of men having chronic pelvic pain syndrome or chronic prostatitis.^[1] However, only 5%-10% of men with symptoms of prostatitis have bacterial prostatitis.^{[18, 19, 20]}  

Symptoms of prostatitis are very common in men aged 36-50 years. In fact, prostatitis is the most common urologic problem in men younger than age 50 years. It is the third most common urologic problem in older men.

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Prognosis

Treatment success rates with the administration of trimethoprim-sulfamethoxazole (TMP-SMZ) approach 30%-40%, while success rates with fluoroquinolones are 40%-75%. Relapses are common and can be treated with another course of antibiotics. If repeat treatment fails, consider a low, suppressive dose of antibiotics.

Infection often persists because antibiotics do not penetrate the prostate easily and no active transport mechanism exists whereby antibiotics can enter the prostatic ducts. Another inhibiting factor is that prostatic fluid is acidic compared with plasma, thus creating a pH gradient that further inhibits diffusion of acidic antibiotics into the prostatic fluid.

Morbidity and mortality

Prostatitis can impair the patient's quality of life to the same degree as coronary artery disease or Crohn disease. Studies show that prostatitis has the same effect on a patient's mental health as do diabetes mellitus and chronic heart failure.^[21]

A retrospective study suggested that a relationship exists between the severity of chronic prostatitis symptoms and erectile dysfunction frequency. Whether this relationship is mediated through organic or psychological mechanisms has remained unclear.^[22] In a comparison of data from 317 patients with chronic bacterial prostatitis (CBP) due to C trachomatis and 639 patients with CBP caused by common uropathogenic bacteria, Cai and colleagues reported that patients with chlamydial CBP reported a higher prevalence of premature ejaculation and lower quality of life.^[23]

Alkan et al reported that levels of superoxide anion and total reactive oxygen species (ROS) were significantly higher in the semen of men with category IIIA chronic prostatitis/chronic pelvic pain syndrome compared with healthy controls, and that those levels correlated negatively with scores on an erectile dysfunction questionnaire. These authors suggest that overproduction of superoxide anion and ROS could be one of the important mechanisms for erectile dysfunction in these patients.^[68]

In a study of 110 infertile men with CBP, the 78 patients who responded to levofloxacin treatment (as indicated by eradication of bacteria from sperm cultures) showed showed a significant increase in sperm progressive motility and a significant decrease in seminal leukocyte count, seminal fluid viscosity, liquefaction time, reactive oxygen species production, and seminal tumor necrosis factor-α and interleukin-6 levels. None of those posttreatment variables were significantly different than those in a control group of 37 fertile men. In the patients with poor antibiotic responsiveness, however, all measured semen variables showed deterioration.^[24]

There is concern that clinical chronic prostatitis may be a risk factor for prostate cancer. Two separate meta-analyses and other large case-control studies have estimated a 60% increased risk of prostate cancer in patients with symptomatic prostatitis in white men.^[25] However, African Americans have been shown in one study to actually have a slightly decreased risk of prostate cancer with symptomatic prostatitis.^[25]

Some studies report that men with prostate cancer have histological prostatic inflammation 4-5 times more often than men without prostate cancer. Other studies have suggested that histological prostatic inflammation in benign prostate tissue specimens from asymptomatic men are associated with decreased future prostate cancer risk.^[25] As mentioned previously, prostatic inflammation is a nonspecific finding, and its relation to prostate cancer is also unclear. 

CBP is not associated with mortality. However, acute bacterial prostatitis represents a potentially lethal process if untreated.

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Patient Education

For patient education information, see the Men's Health Center, as well as Understanding the Male Anatomy, Prostate Infections (Prostatitis), and Urinary Tract Infections (UTIs).

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History

Patients with chronic bacterial prostatitis (CBP) often present with history of recurrent urinary tract infections (UTIs). Presenting complaints may vary from patient to patient, and may include any of the following:

• Dysuria
• Urinary urgency and frequency
• Urinary hesitancy or retention
• Hematuria
• Malodorous urine
• Urethral discharge

Between episodes of acute infections, some patients are asymptomatic, while others may describe a long history of persistent symptoms similar to chronic prostatitis/pelvic pain syndrome (CPPS). Fevers and chills are uncommon, as they are typically seen only with acute bacterial prostatitis. 

A sexual history should also be taken. Specifically, the patient should be queried about multiple partners, unprotected anal intercourse, and the possibility of sexually transmitted diseases.

Patients with CBP and persistent symptoms similar to CPPS may present with a wide range of signs and symptoms. The four main domains of prostatitis symptoms include the following^[26] :

• Genitourinary pain
• Lower urinary tract symptoms (LUTS)
• Psychological issues
• Sexual dysfunction​

Genitourinary pain will most commonly will be in the perineum (roughly 63%), testicles, suprapubic area, and penis (especially the penile tip), but can also include the groins, rectum, lower abdomen, or low back. Pain may also occur or increase during urination or ejaculation. Neuropathic pain can also contribute to symptoms.

LUTS may include obstructive storage symptoms or voiding symptoms. Obstructive storage urologic symptoms include the following:

• Urinary frequency
• Urgency or urge incontinence
• Hesitancy
• Dysuria
• Nocturia
• Postvoid dribbling

Voiding symptoms include the following:

• Weak stream
• Straining
• Urinary hesitancy

Recurrent episodes of acute UTI with LUTS is typical for CBP. Patients who have these symptoms persistently are more likely to have CPPS. 

Psychological issues associated with prostatitis include the following:

• Depression
• Anxiety or stress
• Overall decreased quality of life
• Cognitive or behavioral deficits

Sexual dysfunction associated with prostatitis includes the following{ref14]:

• Ejaculatory pain
• Hematospermia
• Erectile dysfunction
• Decreased libido
• Premature or delayed ejaculation

In patients with persistent symptoms, further evaluation should be done to assess their quality of life, functional status, and satisfaction with care. The National Institutes of Health's Chronic Prostatitis Collaborative Research Network developed a symptom index that is widely used for clinical evaluation and research. It has been accepted by the international prostatitis research community and shown to be reliable in primary care and clinical trials.^{[27, 28, 7]}

The National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) covers the three most important domains of chronic prostatitis with nine questions. The first domain, pain, is captured in four questions covering location, severity, and frequency. The second domain, urinary function, is captured in two questions covering irritative storage symptoms and obstructive voiding function. The third domain, quality of life, is captured in three questions covering how the symptoms effect daily activities. The NIH-CPSI is pictured below.

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US National Institutes of Health chronic prostatitis symptom index.

Other validated symptom-scoring instruments that can be used to evaluate patients and monitor response to interventions include the International Prostate Symptoms Score (IPPS) and the Urinary, Psychosocial, Organ-specific, Infection, Neurological/systemic, Tenderness (UPOINT) classification. IPPS is an eight-item questionnaire that evaluates urinary symptoms and impact on quality of life. UPOINT classification helps to stratify patients into phenotypes based on their symptoms and has been used to phenotypically direct multimodal treatment in CPPS.^[29]

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Physical Examination

Physical examination is important and should be helpful in classifying the disorder, which guides therapy. Findings in CBP, similar to CPPS, may be normal except for localized tenderness and pain. 

Prostate examination by digital rectal examination (DRE) shoud be done after collection of preprostatic massage urine specimens. The prostate may be normal in size and consistency or may seem slightly boggy. Pain during prostate examination is variable and unhelpful for classifying the type of prostatitis.^[1]  In contrast, acute bacterial prostatitis is characterized by a very tender, warm, swollen, boggy gland. When acute bacterial prostatitis is suspected, prostate massage should be avoided because of the risk of causing bacteremia.

Prostatic calculi are rarely palpable on prostate examination because they are typically located deep within the prostate gland. If calculi are palpable they are a significant clue to the cause of the recurrences, because they can be a nidus for infection.

Pelvic floor muscle dysfunction can also be evaluated by palpating the deep muscles duirng DRE and the perineum and superficial pelvic floor muscles externally. The strength and endurance of muscles, quality and timing of contractions, and ability to relax the muscles between contractions should be evaluated. 

An abdominal exam should also be done, to help exclude other causes of pain. A palpable bladder may be appreciated if the patient has urinary retention. 

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Approach Considerations

Most cases of chronic bacterial prostatitis (CBP) can be diagnosed with history, physical examination, and urine or semen culture.  A urine dipstick is often done as the same time as urine culture collection to evaluate for signs of infection and hematuria. 

The formal diagnosis of CBP includes a history of  recurrent urinary tract infections (UTIs) and a 10-fold increase in bacteria in expressed prostatic secretion (EPS), post-massage urine, or semen culture.^[30]  As discussed below, the "four-glass test" to collect EPS is the gold standard for diagnosis, but this test is cumbersome and not widely used in the clinical setting; often a urine or semen culture is adequate for diagnosis. 

If urine or semen cultures are not diagnostic and the patient has symptoms suggestive of CPPS, additional tools are recommended for evaluation, including the following:

• UTI localization test (two-glass)
• Urinary flow rate
• Postvoid residual determination
• Urine cytology

To exclude other diagnoses on the differential such as infections, stones, abscesses, obstruction, or prostate cancer, further tests can be done, including the following:

• Urethral swab and culture 
• Screening for sexually transmitted infections 
• Prostate-specific antigen (PSA) testing 
• Uroflowmetry 
• Retrograde urethrography 
• Cystoscopy 
• Prostate biopsy 
• Transrectal ultrasound 
• Renal ultrasound 
• Prostate biopsy 
• Magnetic resonance imaging (MRI) or computed tomography (CT) scan 

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Prostatic Massage

The prostatic massage is needed to collect an expressed prostatic specimen (EPS) or post-massage urine to help localize the bacterial infection. It is done during the rectal examination by kneading the prostate from front to back and from lateral to medial until a milky fluid is obtained from the urethra. This may require as long as a minute of fairly vigorous massage and the patient should be informed of this. Please refer to Diagnostic Prostatic Massage / Technique/Approach Considerations for more details on performing prostatic massage.

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Urinary Tract Localization Tests

Collecting urine specimens before, during, and after prostatic massage can help localize the bacterial infection within the urinary tract. The traditional four-glass urine collection technique, as described by Meares and Stamey in 1968, includes examination of four urine specimens. The collection procedure is as follows:

1. The first specimen is voided bladder–1 (VB1), which is the first 10 mL of urine and represents the urethral specimen.
2. The patient then voids another 100-150 mL of urine.
3. The second specimen, voided bladder–2 (VB2), is collected, which is another 10 mL of urine and represents the bladder specimen.
4. The third specimen is the expressed prostatic specimen (EPS), which is the fluid collected during prostatic massage.
5. The fourth specimen, voided bladder–3 (VB3), consists of the first 10 mL of urine collected after EPS; it contains any EPS trapped in the prostatic urethra.

All four specimens are sent for culture.^[5] The three urine specimens are centrifuged and the sediment is examined with microscopy to identify signs of inflammation, including white blood cells/aggregates, macrophages, oval fat bodies, bacteria and fungal hypha. A wet mount can be used to examine the EPS with microscopy, as well. 

The two-glass test, also known as pre-massage and post-massage test, is simple and cost-effective. It is used more commonly in clinical practice to screen patient with prostatitis. The pre-massage urine specimen is midstream catch and the post-massage urine specimen is the initial 10 mL after prostatic massage. The sediment is evaluated with microscopy and the urine is cultured. See the image below.

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Urine culture with greater than 100,000 colony-forming units (CFU) of Escherichia coli, the most common pathogen in acute and chronic prostatitis. Chr....

If infection is present but localization of the infection is not possible, which suggests acute cystitis, the patient can be treated with nitrofurantoin or another antibiotic that does not penetrate the prostate well, to clear the infection from the urine, and the procedure can then be repeated. If bacteria are subsequently localized to the EPS or VB3, then CBP can be diagnosed.

CBP is also associated with prostatic inflammation, which is 10 or more white blood cells per high-power field (WBCs/HPF). This is not a specific finding; it is commonly associated with nonbacterial prostatitis, asymptomatic inflammatory prostatitis, urethritis, prostatic stones, or recent ejaculation and therefore does not add significant clinical information to aid in diagnosis.

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Semen culture

Semen cultures are a simpler test than the gold standard four-glass test. The sensitivity of semen cultures for diagnosing CBP has been reported between 10%-100%.^[31] The significance and diagnostic value of semen culture remains controversial and further studies are needed to determine whether semen culture alone may represent a reasonable diagnostic alternative.

Budia et al retrospectively studied 895 patients with chronic prostatitis/CPPS who all had EPS and/or VB3 specimens as well as semen cultures done. They reported that semen cultures had higher sensitivity than EPS samples for gram-negative organisms (97% versus 82.4%) and for gram-positive cultures (100% versus 16.1%).^[32]

Magri et al conducted a retrospective study of 696 patients with prostatitis symptoms who had a four-glass test and semen culture analyzed for bacteriological work-up. They found that semen cultures are a useful adjunctive diagnostic tool and there were no differences in eradication rates (using combination treatment with a fluoroquinolone and a macrolide) between patients diagnosed with different tests.^[33]  

Zegarra Montes et al conducted a prospective comparison of diagnosis with a semen culture versus diagnosis with the four-glass test, in 70 men with symptoms consistent with chronic prostatitis along with 17 asymptomatic controls. Semen culture had a sensitivity of 45% and specificity of 94%.These authors concluded that a positive semen culture in a symptomatic patient may be sufficient to justify starting treatment with antibiotics but a negative culture does not rule out CBP.^[31]

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Prostate-Specific Antigen Testing

Routine PSA testing during a prostatitis episode is not recommended. Most patients with clinically proven bacterial prostatitis have an elevated PSA value independent of any cancer-related elevation. No prostatitis-adjusted tables are available to indicate which PSA values are inappropriate in this patient population.

In patients with bacterial prostatitis who have an elevated PSA value, a reevaluation of the PSA value 6-8 weeks after appropriate treatment is recommended to ensure the value is decreasing to normal levels. It is also appropriate to review the patient’s recent PSA values as a point of comparison. If values remain elevated after appropriate therapy, prostate biopsy is recommended to rule out concomitant pathology.

PSA testing should be considered to exclude prostate cancer only if the findings on digital rectal examination (DRE) raise concern. If PSA testing is done, it should be postponed as  follows:

• After DRE - 1 week
• After treatment for a UTI -  6 weeks
• After prostate biopsy - 6 weeks
• After vigorous exercise or sexual intercourse - 48 hours

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Imaging Studies

Retrograde urethrography

Retrograde urethrography is performed to help confirm the presence of a urethral stricture and evaluate its severity. It is performed by injecting contrast into the urethral meatus and obtaining pelvic radiography. If a stricture is present, narrowing of urethral caliber is observed.

Transrectal ultrasound 

Transrectal ultrasonography of the prostate cannot be used to formally diagnose CBP. Although hypoechoic lesions representing calcifications within prostate may suggest the infection and inflammation associated with CBP, these findings are highly nonspecific. Transrectal ultrasonography findings may also help to identify prostatic stones. In certain patients with frequent recurrences, these stones may be a contributing factor in CBP.

Transrectal ultrasound is useful only if a prostatic abscess exists. Abscesses are extremely rare, but if they are present, patients may also have a high fever and appear quite ill. CT scanning may also be helpful in this situation if transrectal ultrasonography is not available. MRI may also be used but is not as readily available in most acute situations.

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Other Tests

Uroflowmetry

Uroflowmetry is a simple urodynamic test to help evaluate the rate of urine flow over time. It is used in patients with prostatitis to help evaluate for obstruction secondary to a urethral stricture or prostatic enlargement. Results are obtained in graphic form. Normal results show a rapid rise to a peak and then a gradual drop-off back to baseline.

A urethral stricture is indicated by a rapid rise to a low point, a plateau for the remainder of the study, and then a drop-off at the termination of the study. In prostatic enlargement, a wide variety of patterns may be present, but the peak flow is usually less than 15 mL/s, and a stop-start pattern may also be present. To help delineate abnormalities and to differentiate a stricture from prostatic enlargement, cystoscopy should be performed.

Postvoid residual testing

Postvoid residual testing measures the volume of urine left in the bladder immediately after voiding. This volume can be measured by catheterizing the bladder or by using a bladder scanner. Although the results are nonspecific, they can give clues to the presence of lower tract dysfunction, which may require surgical intervention to relieve prostatic obstruction or urethral stricture.

Urodynamics

If patients have not responded to standard therapy or they have abnormalities on uroflometry or postvoid residual tests, further urodynamic studies may provide more information or diagnose a chronic voiding dysfunction. Video-urodynamics can be used to evaluate patient with storage or voiding symptoms to look for urethral obstruction, abnormalities of vesical neck, external sphincter dyssynegia, detrusor overactivity, or acontractile bladder. In patients with classic CBP symptoms, urodynamic studies may not provide any useful diagnostic information. 

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Procedures

Prostate Biopsy

This is the most definitive, but least practical, modality used to diagnose bacterial prostatitis. The biopsy sample can serve as a specimen for culture, which if positive provides a definitive diagnosis. Viewing the sample under microscopy can help to identify a focal infiltration of inflammatory cells into the prostatic stroma. Again, the finding of inflammation is not specific to CBP. Category IV prostatitis is sometimes diagnosed using prostate biopsy. Category IV prostatitis is asymptomatic but may be responsible for elevations in PSA levels, resulting in the need for a diagnostic biopsy to help exclude prostate cancer.

However, prostate biopsy carries a risk of complications, including bleeding, injury to surrounding structures, and infection. In the face of an active infection such as acute prostatitis, performing a biopsy could precipitate sepsis. Overall, prostate biopsy is not recommended as a diagnostic modality for CBP and should be done only if prostate cancer is suspected on the basis of PSA level and/or DRE findings. 

Endoscopy (Cystoscopy)

Lower urinary tract endoscopy (cystoscopy) is only indicated for patients with concern for lower urinary tract malignancy (hematuria), stones, urethral strictures, bladder neck abnormalities or other surgically corrected abnormalities. It may be justified in patients in whom standard therapy has failed, but clinical experience suggests that it is not indicated for most men with chronic prostatitis.^[1]

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Histologic Findings

Prostatitis, from a pathologist standpoint, is an increased number of inflammatory cells within the prostatic parenchyma. As with inflammatory markers in urine, inflammation of the prostate is not specific to prostatitis and can be found in patients without prostate disease. Therefore, biopsy is rarely used to diagnose prostatitis. Biopsies done to evaluate for prostate cancer commonly show chronic inflammation and if patients area asymptomatic they are categorized as IV prostatitis (asymptomatic inflammatory prostatitis) (See the image below.)

View Image

A nonspecific, mixed inflammatory infiltrate that consists of lymphocytes, plasma cells, and histiocytes is typical in chronic bacterial prostatitis.

Inflammation of the prostate tends most commonly follows a pattern of stromal lymphocytic infiltrates adjacent to acini, but varies and may also include glandular or periglandular inflammation in patient with chronic prostatitis. ^[1]

Prostatic calculi may also be associated with inflammation as they obstruct prostatic ducts limiting drainage or provide a nidus for bacteria, which can contribute to inflammation. 

• References

Approach Considerations

Antibiotics are the most common therapy used to treat chronic bacterial prostatitis (CBP). Eradication of bacteria is associated with clinical success in the short and long term with CBP caused by both traditional and nontraditional bacteria.

Studies have shown that patients with a recent diagnosis of prostatitis who are antibiotic-naive have an excellent symptomatic response, regardless of culture status.^{[34, 35]} In contrast, men with chronic prostatitis or chronic pelvic pain syndrome (CPPS) of long duration who have been previously treated are not likely to have symptom improvement with a course of antibiotics, and therefore should not be given antibiotics.^[1] Antibiotic therapy can be used in an attempt to cure CBP but relapses are common. CBP in men with prostatic calculi is more difficult to cure. 

Fluoroquinolones are the mainstay in the treatment of CBP. Fosfomycin has been shown to have good activity against extended-spectrum beta-lactamase producing organisms. Azithromycin may be more effective for Chlamydia infections. Most other antimicrobial agents are unlikely to eradicate the infection. 

Although bacteria are cultured in only 5%-10% of prostatitis cases, bacteria may still be the cause of the chronic prostatitis in many patients with the syndrome. Studies using extensive research methods (eg, reverse transcriptase polymerase chain reaction assay) show evidence of bacterial infection in some patients despite negative urine cultures. Negative culture results occur for various reasons, including insufficient sample volume, initiation of antibiotics prior to obtaining an expressed prostatic secretion sample, and the presence of fastidious organisms.

In such cases, patients often have improvement in symptoms with antibiotic treatment. Thus, if clinical evidence strongly suggests chronic prostatitis in a patient with negative cultures, a 2-week trial of antibiotics is worthwhile. If the symptoms improve, prescribe a complete course of antibiotics. 

In most cases, symptomatic treatment with analgesics and alpha blockers may be used to help alleviate symptoms. Sitz baths also may provide symptomatic improvement.

Surgery is usually not indicated for chronic prostatitis. However, in select situations when a patient has episodes of chronic prostatitis that improve with antibiotics but then recur, transurethral resection of the prostate (TURP) or transurethral vaporization of the prostate (TUVP) may remove a nidus of infection. This nidus may be in the form of prostatic stones. These stones are usually visible on transrectal ultrasonograms.^[36]

Other therapies used to treat CPPS may provide symptomatic improvement for CBP but have not been studied extensively in the CBP population. These other therapies include the following^{[37, 1, 26, 29, 70]} : 

• Physiotherapy with myofascial release and paradoxical relaxation
• Biofeedback, transcutaneous electrical nerve stimulation (TENS), acupuncture 
• Medications for neuropathic pain (gabapentinoids, antidepressants) 
• Psychotherapy
• Neuromodulation procedures (spinal cord or sacral nerve root stimulation) 
• Bladder retraining 
• Therapeutic ejaculation 

A meta-analysis concluded that viewing chronic prostatitis/CPPS as a psycho-neuromuscular disorder driven by protective pelvic floor guarding and psychosocial stress, and treating with techniques such as myofascial trigger point release, biofeedback, and cognitive-behavioral therapy, can result in clinically significant improvement in symptoms.^[69]

• References

Antimicrobial Therapy

The choice of antimicrobial is critical because the prostate has an epithelial lining and a pH gradient that inhibits antimicrobials from entering the prostatic acini. Ideal antibiotics have a higher dissociation constant to allow diffusion of their non-ionized components into the prostate. In addition, if the antibiotic has a basic pH, it can readily reach much higher concentrations in prostatic fluid than in the plasma because of the pH gradient. Agents able to reach sufficient concentrations in prostatic tissue include fluoroquinolones, macrolides, tetracyclines, and trimethoprim. 

The choice of antibiotics for treatment should also be guided by urine bacterial cultures and sensitivities. It is important to use an antibiotic with broad-spectrum coverage because many different bacteria have been isolated in the prostate, although gram-negative Enterobacteriaceae group are the most common. 

Antibiotic therapy begins with initial 4- to 6-week course. A second course of 4-6 weeks can be offered if a bacterial cause is confirmed or the first course resulted in a partial symptomatic response.

If bacterial cultures remain positive, longer treatment is necessary. The best results have been observed with a 12-week course of therapy, although maintaining patient compliance may be difficult with longer durations of treatment.

A second cycle of antibiotics can be considered if initial treatment fails, because according to some authors up to 20% of patients in whom initial treatment failed may be rescued by using a second cycle.^[1] If the patient obtains no obvious symptomatic benefit from infection control or cultures are negative, repeated use of antibiotics should be avoided.^[26]

Fluoroquinolones

The antibiotics of choice are the fluoroquinolones (eg, ciprofloxacin, levofloxacin, ofloxacin, moxifloxacin), due to their favorable pharmacokinetic properties and broad-spectrum activity. Fluoroquinolones have demonstrated high bactericidal activity against the Enterobacteriaceae group of bacteria and against Pseudomonas aeruginosa. They also have activity against chlamydial and gonococcal organisms. However, fluoroquinolones are generally ineffective against streptococci, enterococci, and anaerobes.

Reported microbiological eradication rates are 40%-70% for ciprofloxacin and 75% for levofloxacin. One comparative study of patients with CBP concluded that levofloxacin 500 mg once daily is as effective as ciprofloxacin 500 mg twice daily for 4 weeks^[38] A similar study found that compared with ciprofloxacin, levofloxacin produced higher rates of bacterial clearance and clinical improvement, as well as lower rates of microbiological recurrence.^[39]

In contrast, a systematic review of 18 studies reported no significant differences in clinical improvement, microbiological eradication, or rate of adverse effects among oral fluoroquinolones, including ciprofloxacin, levofloxacin, lomefloxacin, ofloxacin, and prulifloxacin.^[40] The optimal duration of fluoroquinolone treatment for CBP caused by traditional organisms is not well studied and more research is needed optimize doses and lengths of antibiotics being prescribed. 

Fluoroquinolone therapy is not always feasible in patients with contraindications such as long QT syndrome or tendonitis. Reported resistance rates to fluoroquinolones in Enterobacteriaceae causing urinary tract or intra-abdominal infections have increased in previous years and exceed 50% in some parts of the world, especially Asia. In Europe and North America, resistance rates range from less than 10% in rural areas to more than 30% in sexual networks.^[41]

National and international antibiotic stewardship practices have helped to lower the percentage of ciprofloxacin-resistant extended-spectrum β-lactamase (ESBL) Enterobacteriaceae in urinary isolates in both hospital and community settings.^[42] Nevertheless, alternative antibiotics for treating CBP are needed. 

Trimethoprim/sulfamethoxazole

Trimethoprim/sulfamethoxazole (TMP/SMX) or even trimethoprim alone were widely used in the 1970s to 1990s. Eradication rates ranged from 0% to 67%, with most studies reporting rates of 30%-50% with a 4- to 6-week course of treatment. Longer duration of therapy, around 90 days, provides best clinical results. TMP/SMX does have good penetration into the prostate and activity against most relevant pathogens but resistance rates are high. It does not have activity against Pseudomonas,Chlamydia, or gonococci. Overall, TMP/SMX is less effective for bacterial eradication than fluoroquinolones.^[1]

Azithromycin

Azithromycin, a macrolide antibiotic, has reported eradication rates of around 80%.^[20] It has good penetration into the prostate and is active against gram-positive bacteria and Chlamydia. It should not be used as a first-line antibiotic but can be used when microbiological studies identify susceptible pathogens. For Chlamydia infections, azithromycin has been reported to be superior to ciprofloxacin with respect to clinical response and eradication rates.^[40] Clarithromycin, another macrolide antibiotic, is equivalent to azithromycin in both clinical response and eradication rates.^[40]

Fosfomycin

Fosfomycin achieves reasonable tissues levels in the prostate and should be considered in patients with multidrug-resistant gram-negative bacteria on cultures. Fosfomycin is more active in an acidic environment, so the alkaline pH seen during CBP may decrease its activity.

Case reports have documented successful use of fosfomycin for treatment of prostatitis caused by multidrug-resistant gram-negative bacilli.^{[43, 71]} A single case report describes successful use of the combination of fosfomycin and doxycycline to treat persistent prostatitis from ESBL-positive Escherichia coli that was refractory to prolonged courses of fosfomycin alone.^[44]

Los-Arcos et al reported on the use of fosfomycin-tromethamine in 15 patients with CBP (five with multi-drug–resistant Enterobacteriaceae [MDRE] infection) that had proved difficult to treat because of adverse effects or resistance to ciprofloxacin and cotrimoxazole. The patients received 3 g every 48-72 h for 6 weeks. After a median follow-up of 20 months, seven of the patients (47%) had clinical responses and eight (53%) had persistent microbiological eradication; four of the five patients with MDRE isolates achieved eradication. None of the patients experienced adverse effects.^[45]

Other antibiotics 

Doxycycline, a tetracycline antibiotic, has good activity against Chlamydia and Mycoplasma but unreliable activity against Enterobacteriaceae and staphylococci and no activity against Pseudomonas. It has no conclusive role in the treatment of CBP. 

Carbenicillin may be effective for Enterobacteriaceae or Pseudomonas infections. Large-scale studies are not available. Other penicillin derivatives, while effective against gram-positive organisms, are generally ineffective in treating bacterial prostatitis because of poor prostate penetration.

Aminoglycoside antibiotics have been suggested as a possible alternative for CBP treatment. They are one of the recommended agents for treatment of acute bacterial prostatitis.

In a study of 78 men with fluoroquinolone-resistant CBP or contraindications to fluoroquinolone therapy, Vittorio et al reported that intramuscular netilmicin once daily for 4 weeks produced a 78.6% eradication rate and significant reductions in the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) score at 6-month and 12-month followup in those with eradicated infections. Genetic testing for deafness-predisposing mitochondrial mutations guided safer administration and overall therapy was well tolerated.^[46] Further randomized controlled studies are needed to verify aminoglycosides as a therapeutic alternative. 

Ureaplasma infections can be treated with ofloxacin, minocycline, azithromycin, or doxycycline. Those agents all produce similar rates of clinical improvement and microbiological eradication and have similar toxicity profiles.^[40]

Nanobacteria have been implicated in stone formation within the urinary tract, so eliminating them may improve to chronic prostatitis symptoms. Preliminary findings suggest that anti-nanobacterial therapy improves symptoms and decreases or eliminates prostatic calculi in patients with CPPS that is recalcitrant to standard therapy. Further investigation is needed.^[47]

Suppressive antibiotics

Patients with persistent or recurrent infections, especially those who have symptom improvement while on antibiotics but who quickly have a recurrence after finishing a course of antibiotics, may benefit from suppressive therapy with low-dose daily prophylactic antibiotics. Clinical studies have not confirmed the value of suppressive therapy in this setting, but it is widely used.^[1] Good choices are tetracycline, nitrofurantoin, nalidixic acid, cephalexin, and trimethoprim. Bacteria in CBP are usually sensitive strains, even after a number of antibiotic treatment regimens have been tried.

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Additional Treatments

In a meta-analysis of randomized, controlled trials of pharmacologic therapy for the treatment of chronic prostatitis and chronic pelvic pain syndrome, Anothaisintawee et al concluded that alpha blockers and antibiotics, as well as combinations of these therapies, appear to achieve the greatest improvement in NIH-CPSI scores (total, pain, voiding symptoms, and quality of life) compared with placebo. Anti-inflammatory therapies had a lesser, but measurable, benefit on selected outcomes; however, the investigators noted that sample sizes in many studies were small and that publication bias might have overestimated the benefits reported.^[48]

Another systemic review and meta-analysis on therapuetic interventions for patients with chronic prostatitis and chronic pelvic pain syndrome, concluded that the macrolide antibiotic mepartricin, percutaneous tibial nerve stimulation, and triple therapy (with doxazosin, ibuprofen, and the muscle relaxant thiocolchicoside) resulted in both clinically and statistically significant improvements in total NIH-CPSI scores. But they did not find statistically or clinically significant reductions in NIH-CPSI with alpha blockers, antibiotics, or combinations of the two.^[49] Many of these studies included mostly patients with CPPS (negative cultures), and therefore more studies with patients who have CBP are needed. 

Alpha blockers

Alpha-adrenergic antagonist medications include tamsulosin, alfuzosin, doxazosin, terazosin, and silodosin. The uroselective alpha blockers (tamsulosin, alfuzosin, and silodosin) have better adverse-effect profiles and should be first-line choices. The alpha blockers can help to decrease recurrences by diminishing urinary outflow obstruction due to prostate enlargement or congestion secondary to inflammation and improve urinary flow or diminish intraprostatic ductal reflux. 

These agents have provided significant symptom reduction and improvement in quality of life in patients with CBP, as well as those with CPPS. Ten randomized controlled studies evaluating alpha blockers in patients with prostatitis symptoms, mostly in men with CPPS, have been published, with eight of them reporting positive results, using the NIH-CPSI or other validated symptom-scoring tools.

Experts advise that alpha blockers should be considered as part of initial treatment of patients presenting with lower urinary tract symptoms (LUTS), although there is insufficient evidence to inform best practice with these medications.^[26] Alpha blockers should be used as part of a multimodal approach to treatment in a newly diagnosed patient, but are not recommended as monotherapy, especially if the patient has previously been treated with alpha blockers.^[1] If no relief of symptoms is achieved in 4-6 weeks then the treatment should be discontinued. 

Pain medications

Nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids should theoretically improve inflammation within the prostate to help reduce symptoms, and studies suggest that these agents may be useful as adjunctive therapy for patients with chronic prostatitis.

Cyclooxygenase-2 inhibitors (eg, rofecoxib, celecoxib), which are used for treating other chronic inflammatory conditions, have been used by urologists for prostatitis, with some anecdotal success reported. High-dose rofecoxib was shown to improve symptoms, but this drug has been withdrawn from the market.^[26] Celecoxib has been shown to provide significant symptomatic improvement in patients with CPPS, in a dose-dependent fashion, but benefits are limited to therapy duration.^{[50, 51]}

One meta-analysis reported that NSAIDs (rofecoxib, celecoxib, and a corticosteroid) are 80% more likely to achieve a favorable response, compared with placebo.^[48] However, another meta-analysis of only rofecoxib and celecoxib found no significant difference in response to NSAIDs versus placebo.^[49] Overall, high-dose long-duration therapy with cyclooxygenase-2 inhibitors is not recommended for CBP. 

Pregabalin, a neuropathic pain medication, has been suggested for use in chronic prostatitis and CPPS. In a randomized, double-blind, placebo-controlled trial of 218 men by Pontari et al, 47.2% of men who received pregabalin had a decrease in NIH-CPSI total score; however, the decrease was not statistically significant, and pregabalin was not superior to placebo.^[52]

Opioid analgesics have not been evaluated in chronic prostatitis but are unlikely to provide clinical benefit and pose a high risk of addiction. 

5-alpha-reductase inhibitor

Treatment with 5-alpha-reductase inhibitors (eg, finasteride, dutasteride) has been shown to be effective in relieving symptoms of prostatitis. In the REDUCE study, which was originally designed to evaluate whether treatment with dutasteride decreased prostate cancer risk in men with an elevated PSA, long-term use of dutasteride significantly reduced prostatitis-like symptoms, compared with placebo.^[53]

A randomized, placebo-controlled pilot study by Nickel et al suggested that some men with category IIIA CPPS experience symptomatic improvement with finasteride. However, these authors concluded that the results did not justify recommending finasteride as monotherapy, except for men who also have benign prostatic hyperplasia.^[54]

Supplements

Saw palmetto, an herbal supplement well known as a treatment for prostatic enlargement, has also been used for prostatitis.^[55]  Saw palmetto is hypothesized to act similarly to 5-alpha-reductase inhibitors.

Quercetin, a polyphenolic flavonoid with antioxidant properties found in green tea, onions, and oranges, has also has been shown to significantly decrease symptoms.^[56]

While zinc supplements have been suggested as a medical therapy, clinical results have not been significant. A zinc-containing polypeptide called prostatic antibacterial factor (PAF) may be an important antimicrobial factor within the prostate.

Other treatment modalities 

The role of ejaculation in the treatment of chronic bacterial prostatitis (CBP) is unknown. One theory is that frequent ejaculation may help to clear prostatitic secretions, thereby allowing for quicker resolution. Instruct the patient to ejaculate a minimum of every 3 days, either through intercourse or masturbation, while on antibiotic therapy to help with drainage of the prostatic ducts.

A double-blind, randomized, placebo-controlled study in 60 consecutive patients with CPPS refractory to medical therapy found that transurethral intraprostatic injection of botulinum neurotoxin type A reduced pain and improved quality of life. By 6 months after treatment, pain had decreased almost 80% from baseline in the treated group.^[57]

Daily sitz baths and perianal massage may help with the discomfort associated with chronic prostatitis.

Frequent prostate massage was used extensively several decades ago and its use is still advocated by some in the treatment of difficult cases with persistent positive cultures despite appropriate antibiotic therapy.

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Consultations

Consultation with a urologist may be appropriate for men with relapsing chronic bacterial prostatitis (CBP) or for situations in which the diagnosis is unclear. A urologist may be able to properly perform the bacterial localization studies necessary to diagnose CBP (see Workup/Urinary Tract Localization Tests).

In the author's experience, most primary care physicians are not comfortable or experienced with obtaining the necessary specimens. Semen cultures or the 2-cup test with urine cultures collected before and following prostatic massage are simpler and represent effective alternatives to the 4-cup test.

Involvement of a multidisciplinary team approach has been recommended by the Prostatitis Expert Reference Group for patients who do not respond to initial treatments. The team may include urologists, pain specialists, nurse specialists, physiotherapists, cognitive behavioral therapists or psychologists, sexual health specialists, and general practitioners.^[26]  Especially in patients with persistent pain, referral to pain specialists to target neuropathic pain should be considered. 

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Surgical Care

Surgery is usually not indicated for chronic prostatitis. However, in select situations when a patient has recurrent episodes of chronic prostatitis and improves with antibiotics, transurethral resection of the prostate (TURP) or transurethral vaporization of the prostate (TUVP) may remove a nidus of infection. This nidus may be in the form of prostatic stones, which are difficult to treat with antibiotic therapy alone. These stones are usually visible on transrectal ultrasonograms.

TURP/TUVP is performed in a standard fashion after preoperative antibiotics have been administered. Routine preoperative evaluation should be performed when planning for TURP/TUVP, and routine postoperative care for TURP/TUVP should be administered in these patients.

Prostatectomy

Prostatectomy is rarely indicated in the treatment of chronic bacterial prostatitis (CBP). When used, radical transurethral prostatectomy is suggested. This procedure may be more effective in men with prostatic calculi. Because most of the inflammation is located in the peripheral zone of the gland, an extensive resection of the gland is required to remove all infected and potentially infected tissue down to the level of the true prostatic capsule.

Only a single series of 10 patients, most with prostatic calculi, has been reported, but all 10 were considered cured.^[58]  These authors concluded that the procedure is indicated, although only rarely, in men with well-documented bacterial infections in whom medical pharmacotherapy fails for 1 year.

For refractory cases, other authorities have suggested that transurethral microwave therapy to ablate prostate tissue has shown some benefit.^[59]  At this time, this intervention should be considered only in patients in whom less-invasive therapies have failed but who do not desire radical transurethral prostatectomy. Larger series would be helpful to define the benefit of this procedure.

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Diet and Activity

Diet does not have an important role in treating CBP. Some physicians have advocated the avoidance of spicy foods, caffeine-containing products, tobacco and alcohol; however, no evidence has indicated any CBP-associated benefit from this. 

Activity changes do not have a prominent role in the treatment of CBP. However, the authors often advise patients to avoid bicycling or other activities that may put pressure on the perineal region.^[37]

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Long-Term Monitoring

Patients should be followed up 4-6 weeks after initial presentation and further management should be guided by their symptoms.

If the patient is treated long-term with antibiotics, ensure that repeat localization studies of the prostate (ie, pre– and post–prostatic massage urine cultures after treatment) are conducted to conclude that the bacteria have been eliminated. If repeat cultures return positive results, prescribe a second course of antibiotics with a drug that has a different mechanism of action.

If repetitive courses of antibiotics fail but the patient has improved symptoms while on antibiotics, consider long-term, low-dose, suppressive therapy. Alternatives for suppressive therapy include single-strength TMP/SMX (one tablet qhs), trimethoprim (100 mg qhs), ciprofloxacin (250 mg qhs), and ofloxacin (200 mg qhs).

As with CPPS, symptom scores should be used to monitor improvements with different interventions. The following are the most commonly used tools:

• National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI)
• International Prostate Symptoms Score (IPPS)
• Urinary, Psychosocial, Organ-specific, Infection, Neurological/systemic, Tenderness (UPOINT) classification

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Medication Summary

Oral antimicrobial agents are the mainstay of treatment for chronic bacterial prostatitis (CBP), with the most effective medications being fluoroquinolones and trimethoprim-sulfamethoxazole (TMP/SMX). Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.

Alpha blockers, which relax smooth muscle in the bladder neck, can help to decrease recurrences of CBP by diminishing urinary obstruction due to prostate enlargement or congestion secondary to inflammation.

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Ciprofloxacin (Cipro)

• Dosing, Interactions, etc.

Clinical Context:  Ciprofloxacin is a fluoroquinolone with activity against pseudomonas, streptococci, MRSA, Streptococcus epidermidis, and most gram-negative organisms, but with no activity against anaerobes. It inhibits bacterial DNA synthesis and, consequently, growth.

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Moxifloxacin (Avelox)

• Dosing, Interactions, etc.

Clinical Context:  Moxifloxacin is a quinolone that has antimicrobial activity based on its ability to inhibit bacterial deoxyribonucleic acid (DNA) gyrase and topoisomerases, which are required for replication, transcription, and translation of genetic material. Quinolones have broad activity against gram-positive and gram-negative aerobic organisms. Differences in chemical structure between quinolones have resulted in altered levels of activity against different bacteria. Altered chemistry in quinolones results in toxicity differences.

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Trimethoprim and sulfamethoxazole (Bactrim, Bactrim DS, Septra, Septra DS)

• Dosing, Interactions, etc.

Clinical Context:  TMP/SMX inhibits bacterial growth by inhibiting the synthesis of dihydrofolic acid. It has good penetration into the prostate and activity against most relevant organisms. It has no acitivity against Pseudomonas. 

• References

Ofloxacin

• Dosing, Interactions, etc.

Clinical Context:  Ofloxacin penetrates the prostate well and is effective against Neisseria gonorrhea and C trachomatis. It is a derivative of pyridine carboxylic acid with broad-spectrum bactericidal effects.

• References

Doxycycline (Doryx, Periostat, Adoxa, Vibramycin, Oraxyl)

• Dosing, Interactions, etc.

Clinical Context:  Doxycycline inhibits protein synthesis and, thus, bacterial growth by binding to 30S and, possibly, 50S ribosomal subunits of susceptible bacteria. It has good activity against Chlamydia and Mycoplasma. It is contraindicated in renal and liver failure. 

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Gentamicin

• Dosing, Interactions, etc.

Clinical Context:  Gentamicin is an aminoglycoside antibiotic for gram-negative coverage. It is used in combination with an agent against gram-positive organisms and one that covers anaerobes. It is not the drug of choice, but consider its use if other, less toxic drugs are contraindicated, when it is clinically indicated, and in mixed infections caused by susceptible staphylococci and gram-negative organisms.

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Levofloxacin (Levaquin)

• Dosing, Interactions, etc.

Clinical Context:  Levofloxacin is indicated for pseudomonal infections and for infections that are due to multidrug-resistant, gram-negative organisms.

• References

Azithromycin

• Dosing, Interactions, etc.

Clinical Context:  Good penetration into prostate. Covers Chlamydia and gram-positive bacteria but unreliable activity against gram-negative bacteria. 

• References

Class Summary

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting. Fluoroquinolones are frequently used because they are able to concentrate in the prostate and are lipid soluble. Sulfonamides are also used, because they are lipid soluble.

Since 2008 the FDA has issued a Black Box warning regarding the long-term use of fluoroquinolones. There is a risk of tendonitis and tendon rupture that may cause long-term and possibly permanent damage. The occurence is about 1 in 100,000, about 4 times the normal risk. The risk is greatest for the Achilles tendons, but shoulder and hand tendon ruptures also have been reported.

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Terazosin

• Dosing, Interactions, etc.

Clinical Context:  Terazosin is a quinazoline compound that counteracts alpha1-induced adrenergic contractions of the bladder neck, facilitating urinary flow in the presence of prostate inflammation.

• References

Doxazosin (Cardura, Cardura XL)

• Dosing, Interactions, etc.

Clinical Context:  Doxazosin counteracts alpha1-induced adrenergic contractions of the bladder neck, facilitating urinary flow in the presence of prostate inflammation.

• References

Class Summary

These agents relax the smooth muscle to the bladder neck, thus reducing bladder outlet obstruction.

• References

Finasteride (Proscar)

• Dosing, Interactions, etc.

Clinical Context:  Finasteride inhibits the steroid 5-alpha-reductase, which converts testosterone into 5-alpha-DHT, causing serum DHT levels to decrease.

• References

Class Summary

These agents inhibit the conversion of testosterone to dihydrotestosterone (DHT).

• References