Chronic Bacterial Prostatitis

Updated: May 18, 2023
  • Author: Samantha D Kraemer, MD; Chief Editor: Edward David Kim, MD, FACS  more...
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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. In addition, prostatic fluid often displays leukocytosis, 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 expressed prostatic specimen (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.




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 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.


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



The recurrent UTIs in men with 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]


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.



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.



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. [24]

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. [25]

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. [26] However, African Americans have been shown in one study to actually have a slightly decreased risk of prostate cancer with symptomatic prostatitis. [26]

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. [26] 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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