Chronic bacterial prostatitis

https://emedicine.medscape.com/article/458391-overview#showall

Updated: Jul 03, 2017

 Author: Samantha D Kraemer, MD; Chief Editor: Edward David Kim, MD,
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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. 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.
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.
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
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.
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.
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 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]
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.
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).