Chronic bacterial prostatitis represents an infection of the prostate gland. By definition, this condition is characterized by bacterial growth in culture of the expressed prostatic fluid, semen, or postmassage urine specimen. The expressed prostatic secretion (EPS) usually contains more than 10 white blood cells (WBCs) per high-power field (HPF) and macrophages.
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Bacterial prostatitis. Expressed prostatic fluid contains more than 10 white blood cells per high-power field, indicating prostatitis.
The hallmark of chronic bacterial prostatitis is the occurrence of relapsing urinary tract infections, usually involving the same pathogen. Chronic bacterial prostatitis is often confused with nonbacterial prostatitis, chronic pelvic pain syndrome (CPPS), and prostatodynia.
The prostate gland is an accessory sex gland, providing approximately 15% of the ejaculate. The base of the prostate abuts the bladder neck, while the apex is in continuity with the membranous urethra, resting on the urogenital diaphragm.
The adult prostate weighs approximately 20 g but may grow dramatically with age (see Prostate Hyperplasia, Benign). The approximate dimensions are 4.4 cm transversely at the base, 3.4 cm in length, and 2.6 cm in anteroposterior diameter. Antibacterial factors within the prostate, such as zinc, help to prevent infection.
Prostatitis accounts for approximately 2 million annual visits. Twenty-five percent of all men evaluated for urologic problems in the United States are estimated to have symptoms of prostatitis. Approximately 50% of men experience symptoms of prostatitis at some time in their life. However, less than 5-10% of men with symptoms of prostatitis have bacterial prostatitis. Evaluation for these symptoms makes up approximately 8% of all urology visits.
International
Worldwide, 8 million prostatitis-related visits are reported annually.
Mortality/Morbidity
Chronic bacterial prostatitis is not associated with mortality. However, acute bacterial prostatitis (discussed in Acute Bacterial Prostatitis and Prostatic Abscess) represents a potentially lethal process if untreated.
The morbidity associated with chronic bacterial prostatitis is related to its relapsing nature. Chronic bacterial prostatitis may be difficult to eradicate because of the persistence of bacteria within the prostatic acini. Factors that contribute to bacterial persistence include (1) a poor ductal drainage system within the prostate, which can lead to congestion of prostatic secretions, and (2) the tendency for urine to reflux into the prostatic ducts, which may cause irritation and inflammation.
Race
No racial predilections have been identified.
Sex
Bacterial prostatitis affects in males.
Age
Chronic bacterial prostatitis typically affects men aged 40-70 years. Benign prostatic hyperplasia typically affects the same age group.
Relapsing urinary tract infections, interspersed with asymptomatic periods, are common in persons with chronic bacterial prostatitis. Although some men are diagnosed because of asymptomatic bacteriuria, most have varying degrees of irritative voiding symptoms, such as dysuria, frequency, and urgency.
In addition, some patients report feelings of a vague discomfort in the pelvis and perineum. Fevers and chills are uncommon. Rectal palpation of the prostate is not painful and produces no specific findings. Prostatic fluid and postmassage urine cultures, which should be obtained for precise diagnosis, demonstrate bacterial growth.
Characteristics of chronic bacterial prostatitis include the following:
Chronic bacterial prostatitis is the most common cause of relapsing urinary tract infection in males.
Asymptomatic periods are interspersed between episodes of recurrent bacteriuria.
Obstructive or irritative voiding symptoms may occur.
Vague discomfort in pelvis, perineum, lower abdomen, back and testicles is reported.
Physical findings on palpation are often unremarkable.
EPS, postmassage urine culture, or semen culture must be obtained for a precise diagnosis.
Symptoms of prostatitis include the following:
Genitourinary pain
Dysuria and hematospermia
Clear urethral discharge
Recurrent urinary tract infection
The spectrum of organisms grown in culture in chronic bacterial prostatitis is essentially the same as in acute bacterial prostatitis. Most infections are caused by a single pathogen, but a polymicrobial infection is not unusual. Obligate anaerobic bacteria rarely cause prostatic infection.
Localization cultures do not need to demonstrate greater than 100,000 colony-forming units (CFU) per milliliter to establish the diagnosis. Instead, the presence of a greater than 10-fold bacterial growth in the EPS or the third midstream bladder specimen (VB3) compared with the first voided bladder specimen (VB1) and the second midstream bladder specimen (VB2) is important.
Common bacterial pathogens, predominated by gram-negative rods, include the following:
Escherichia coli (80%)
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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....
The physical examination findings, including the findings on prostate examination via digital rectal examination, are typically normal.
The prostate may have areas of firmness related to chronic inflammation. While prostatic calculi are associated with a higher risk of chronic bacterial prostatitis, they are rarely palpable on prostate examination because of their location, which is typically deep within the prostate gland.
In contrast, acute bacterial prostatitis is characterized by a very tender, warm, swollen, firm gland. When acute bacterial prostatitis is suspected, prostate massage should be avoided because of the risk of causing bacteremia.
While chronic bacterial prostatitis may be associated with symptoms of perineal, scrotal, and low back discomfort, the physical examination findings are typically normal.
The actual routes of prostatic infection are unknown in most cases, but various etiologies may be found. 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.
Routes of infection include the following:
Ascending urethral infection
Reflux of infected urine into prostatic ducts
Migration of rectal bacteria via direct extension or lymphogenous spread
Hematogenous infection
The relapsing nature of bacterial prostatitis is due in part to the ductal anatomy of the prostate’s peripheral zone, which prevents dependent drainage of secretions. This can lead to congestion and thickening of prostatic secretions and provides a nidus for recurrent infections. Ductal fibrosis and prostatic calculi, if present, further inhibit the drainage of secretions.
E coli infection accounts for 80% of cases of chronic bacterial prostatitis. The other members of the Enterobacteriaceae family, Klebsiella species, Pseudomonas aeruginosa, and Proteus species are also known pathogens. Chlamydia trachomatis has been implicated as a cause of chronic bacterial prostatitis.[1] However, this organism is unlikely to play a major role in the etiology of chronic bacterial prostatitis.
The role of the gram-positive organisms Staphylococcus epidermitis and Staphylococcus saprophyticus is controversial. These organisms typically colonize the anterior urethra and likely represent contamination when positive in a culture specimen. Only patients in whom a second culture result is positive should receive antibiotic treatment.
Prostatic calculi, although an unspecific finding, often develop in men with chronic bacterial prostatitis; prostatic calculi may serve as a nidus for recurrent infection. A newly described entity termed nanobacteria is thought to play a significant role in urologic stone disease, including prostatic calculi.[2] Nanobacteria may play a role in the chronic nature of this condition. Studies are currently underway to further delineate the role of these organisms in chronic bacterial prostatitis.
The National Institutes of Health (NIH) classification of prostatitis: Based on specific etiologies, the NIH classified the various forms of prostatitis in 1995.[3] The most common type of prostatitis is type III, the chronic pelvic pain syndrome (CPPS) category.
Type I - Acute bacterial prostatitis
Well-defined infectious disease of the lower urinary tract
Bacterial cause, most commonly E coli infection
Frequently presents with bacteremia
Type II - Chronic bacterial prostatitis (focus of this article)
Type III - Chronic abacterial prostatitis (inflammatory CPPS and noninflammatory CPPS)
Most common prostatitis (90% of cases)
Nonbacterial
Diagnosed based on EPS findings, clinical findings, and culture results
Empiric trial of antimicrobials usually warranted (fluoroquinolone or trimethoprim-sulfamethoxazole [TMP-SMZ])
Type IV - Asymptomatic inflammatory prostatitis
Often diagnosed based on results of biopsies, surgical specimens, or semen analysis obtained for other reasons
No treatment warranted
Biopsy typically indicated because of elevated prostate-specific antigen (PSA) level
The various prostatitis syndromes have been classified based on EPS and culture findings. This classification system is important for therapy because the various categories are treated differently. The presence of 10 or more WBCs/HPF in the EPS is considered clinically significant inflammation.
EPS findings are detailed as follows:
Chronic bacterial prostatitis: The EPS usually contains greater than 10 WBCs/HPF and should be obtained. Unlike patients with acute bacterial prostatitis, these patients are not acutely ill.
Acute bacterial prostatitis: EPS should not be obtained because of the risk of potentiating bacteremia. If the EPS is obtained inadvertently, sheets of WBCs are present. The voided urine reveals significant bacterial growth due to accompanying cystitis.
Nonbacterial prostatitis: The prostate is significantly inflamed, as revealed by more than 10 WBCs/HPF. However, routine bacterial culture does not demonstrate growth of organisms. Cultures for fungi, Chlamydia, Ureaplasma, and Mycoplasma rarely demonstrate growth.
Prostatodynia: No inflammation in the EPS or bacterial growth in culture is present. Pelvic-perineal pain appropriately describes the symptoms of this condition.
Historically, the criterion standard for diagnosis is the 3-cup bacterial localization study. This test represents the classic method for the diagnosis of bacterial prostatitis. The technique was described initially by Meares and Stamey in 1968.[4] Clinically, the 3-cup test has proven time-consuming and cumbersome; thus, its use as a diagnostic tool is declining. Obtaining urine cultures prior to and following prostatic massage have arisen as clinically useful alternatives to the 3-cup test. More recently, Magri et al (2009) conducted a retrospective study of semen cultures and found them to be a useful adjunctive diagnostic tool.[5] However, further studies are needed to confirm these findings and to determine if semen culture alone may represent a reasonable diagnostic alternative.
The 3-cup test is performed best when the bladder urine is sterile. If the bladder urine is not sterile, an oral antibiotic such as nitrofurantoin may be prescribed to sterilize the bladder urine. Nitrofurantoin achieves excellent bladder concentrations but does not produce significant intraprostatic levels. The method for performing a 3-cup test is described below.
VB1 represents any bacterial growth within the urethra. The patient is asked to retract the foreskin, if present, and cleanse the meatus. The VB1 is the first 5-10 mL of voided urine and should be collected in a sterile cup.
After the VB1 collection, the patient urinates another 100-150 mL of urine. The next 10-15 mL is collected in a sterile cup and represents VB2, the bladder component of any bacterial growth.
The EPS represents the prostate contribution. The EPS is obtained by massaging and compressing the prostate gland until a drop of fluid is obtained. The EPS is examined under high power in a microscope. More than 10 WBCs/HPF is abnormal and consistent with prostatic inflammation. In addition to WBCs, the EPS may contain oval bodies, which are fat-containing macrophages; these also indicate inflammation.
The VB3 represents a mixture of prostatic fluid and bladder urine. The VB3 is the first 5-10 mL of urine obtained after the prostate massage for the EPS. Similarly, this VB3 is sent for culture.
Imaging studies are not necessary for the diagnosis and treatment of chronic bacterial prostatitis.
Transrectal ultrasonography cannot be used to diagnose chronic bacterial prostatitis. Although hypoechoic lesions and calcifications within the prostate may suggest the infection and inflammation associated with chronic bacterial prostatitis, these findings are highly nonspecific.
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 re-evaluation 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.
If a patient with chronic bacteriuria does not have chronic bacterial prostatitis based on the above modalities, referral to a urologist is advisable. Chronic bacteriuria should prompt an investigation for underlying causes, such as urinary stasis, infection, stones, abscess, and/or obstruction.
In this situation, evaluation of the upper urinary tract with a radiologic imaging study such as an intravenous pyelography (IVP), renal ultrasonography, or CT scanning is often performed.
In addition, chronic bacteriuria in the absence of chronic bacterial prostatitis may prompt evaluation of the bladder with cystoscopy.
Prostate biopsy is not used to diagnose chronic bacterial prostatitis. However, prostate biopsy samples collected to evaluate prostate cancer may demonstrate focal areas of inflammation characterized by a lymphocytic response. The pathology report is often described as chronic prostatitis.
Although this type of finding may suggest chronic bacterial prostatitis, it also may represent nonbacterial prostatitis. The history of chronic urinary tract infections provides the clinical diagnosis.
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A nonspecific mixed inflammatory infiltrate that consists of lymphocytes, plasma cells, and histiocytes is typical in chronic bacterial prostatitis.
The mainstay in the treatment of chronic bacterial prostatitis is the use of oral antimicrobial agents. The most effective medications are fluoroquinolones and TMP-SMZ.
All other oral agents are unlikely to eradicate the pathogenic bacteria successfully within the prostate because of suboptimal tissue penetration. Longer courses of antibiotic use provide better treatment outcomes. Relapse is not uncommon.
Relapsing urinary tract infections are due to poor penetration of most antimicrobial agents into the prostatic fluid and/or bacterial sequestration, which protects bacteria from antimicrobial exposure. Only small-molecular–sized, unionized, lipid-soluble drugs that are not firmly bound to plasma proteins are able to penetrate the epithelial membrane.
Antimicrobial agents that most effectively penetrate into the prostatic fluid, such as fluoroquinolones and TMP-SMZ, are good treatment choices for chronic bacterial prostatitis.
Treatment should be guided by urine culture results. Failure of an initial course of therapy (typically about 4 wk) should prompt longer courses of treatment. Best results have been observed with a 12-week course of therapy, although patient compliance may be difficult with longer durations of treatment.
High bactericidal activity has been demonstrated against the Enterobacteriaceae group of bacteria and P aeruginosa using fluoroquinolones, a class of antimicrobial agents that inhibits bacterial DNA replication and protein synthesis.
Fluoroquinolones are generally ineffective against the streptococci, including enterococcus, and anaerobes. Penicillin derivatives, while effective against gram-positive organisms, are generally ineffective in treating bacterial prostatitis because of poor prostate penetration.
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.
Prostate fluid is also rich in spermine, which has activity against gram-positive bacteria. Other factors of potential importance in prostate fluid include magnesium, calcium, and lysozyme. Other local immune factors are also under investigation.
Barbalias et al (1998) suggested that the use of alpha-blockers in combination with fluoroquinolones would offer significantly superior symptom resolution and bacteriologic cure rates compared with fluoroquinolone treatment alone.[6] Further study is necessary to define the benefit of the addition of alpha-blocker therapy.
Nonsteroidal anti-inflammatory agents and hot sitz baths are often used clinically for symptomatic relief. However, their benefit in bacteriologic eradication of organisms is not established. 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.
Tetracycline, minocycline, and doxycycline have also been used. They are not considered first-line therapy but may be helpful if Pseudomonas infection is present. Paulson and White (1978) reported a 70% bacteriologic cure rate with 4 weeks of minocycline, but the study involved only 10 men, and 30% developed significant vestibular toxicity.[7] More recent studies indicate a 35% bacteriologic cure rate with minocycline.
Penicillins are ineffective, with the exception of carbenicillin indanyl sodium at 500 mg/d. Carbenicillin may be effective for Enterobacteriaceae or Pseudomonas infections. Large-scale studies are not available.
Preliminary findings suggest that antinanobacterial therapy improves symptoms and decreases or eliminates prostatic calculi in patients with chronic bacterial prostatitis that is recalcitrant to standard therapy. Further investigation is needed.
A recent study in rats found that garlic was superior to placebo in terms of anti-inflammatory and antimicrobial effect. This study also demonstrated a statistically significant synergistic effect of ciprofloxacin plus garlic compared with ciprofloxacin alone. Studies in humans are needed to determine if these effects would translate into a clinical setting.[8]
Prostatectomy is rarely indicated in the treatment of chronic bacterial prostatitis. 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 one series of 10 patients, most with prostatic calculi, has been reported, but all men were considered cured.[9] This procedure is indicated, although only rarely, in men with well-documented bacterial infections in whom medical pharmacotherapy fails for one year.
For refractory cases, other authorities have suggested that transurethral microwave therapy to ablate prostate tissue has shown some benefit.[10] At this time, this intervention should be considered only in patients who have failed less-invasive therapies yet do not desire radical transurethral prostatectomy. Larger series would be helpful to define the benefit of this procedure.
Intraprostatic injection of antimicrobial agents is suggested to obtain high concentrations of antimicrobial agents in the prostatic parenchyma. Plomp et al (1980) noted a 66% bacteriologic cure rate with thiamphenicol in 29 men.[11] Jiminez-Cruz et al (1988) noted a 59% cure rate with aminoglycoside injection in 51 men.[12] Unfortunately, these studies have significant methodological flaws, so the conclusions cannot be considered definitive. This technique is rarely used.
Consultation with a urologist may be appropriate for men with relapsing chronic bacterial prostatitis or when the diagnosis is unclear. A urologist may be able to properly perform the bacterial localization studies necessary to diagnose chronic bacterial prostatitis. In the author's experience, most primary care physicians are not comfortable or experienced with obtaining VB1, VB2, EPS, and VB3 specimens. Semen cultures or urine cultures collected before and following prostatic massage are simpler and represent effective alternatives to the 3-cup test.
Diet does not have an important role in treating chronic bacterial prostatitis. Some physicians have advocated the avoidance of spicy and caffeine-containing foods; however, no evidence has indicated any benefit in chronic bacterial prostatitis.
Activity changes do not have a prominent role in the treatment of chronic bacterial prostatitis, although the authors often advise patients to avoid bicycling or other activities that may put pressure on the perineal region.
The role of ejaculation in the treatment of chronic bacterial prostatitis is unknown. One theory is that frequent ejaculation may help clear prostatitic secretions, thereby allowing for quicker resolution.
Clinical Context:
Bactericidal antibiotic that inhibits bacterial DNA synthesis, and consequently growth, by inhibiting DNA-gyrase in susceptible organisms.
Clinical Context:
Inhibits bacterial synthesis of dihydrofolic acid by competing with para -aminobenzoic acid. This results in the inhibition of bacterial growth.
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.
After completion of a 4-week course of a fluoroquinolone or TMP-SMZ, repeating a culture is advisable. The recurrent and persistent nature of chronic bacterial prostatitis encourages efforts for eradication confirmed by negative results on bacterial cultures.
Persistent bacterial growth should be treated with another 4-week trial of antibiotics. Repeat susceptibility testing is necessary.
A final option for chronic bacterial prostatitis that is recalcitrant to the above therapies is long-term antibiotic suppression in an effort to prevent recurrent cystitis.
A recent retrospective study has suggested a relationship between the severity of chronic prostatitis symptoms and erectile dysfunction frequency. Whether this relationship is mediated through organic or psychologic mechanisms remains unclear, and further studies to investigate this relationship would be helpful.[13]
A 4- to 6-week course of TMP-SMZ results in 33-50% bacteriologic cure rates.
A 4- to 6-week course of fluoroquinolone therapy is equally successful as, if not more successful than, TMP-SMX. Weidner et al (1991) reported a 63% durable response rate at 30 months after treatment.[14]
Joe D Mobley III, MD, MPH, Chief Resident Physician, Department of Surgery, Division of Urology, University of Tennessee Graduate School of Medicine/University of Tennessee Medical Center
Disclosure: Nothing to disclose.
Coauthor(s)
Edward David Kim, MD, FACS, Professor of Surgery, Division of Urology, University of Tennessee Graduate School of Medicine; Consulting Staff, University of Tennessee Medical Center
Disclosure: Lilly Consulting fee Consulting; Astellas Consulting fee Speaking and teaching; Indevus Consulting fee Speaking and teaching
Specialty Editors
Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment
Shlomo Raz, MD, Professor, Department of Surgery, Division of Urology, University of California at Los Angeles School of Medicine
Disclosure: Nothing to disclose.
J Stuart Wolf Jr, MD, FACS, David A Bloom Professor of Urology, Director of Division of Minimally Invasive Urology, Department of Urology, University of Michigan
Bradley Fields Schwartz, DO, FACS, Professor of Urology, Director, Center for Laparoscopy and Endourology, Department of Surgery, Southern Illinois University School of Medicine
Meares ET. Chronic bacterial prostatitis: role of transurethral prostatectomy (TURP) in therapy. In: Schmiedt E, Alken JE, Bauer HW, eds. Therapy of prostatitis. Munich, Germany: Zuckerschwerdt Verlag; 1986:193-197.
Bacterial prostatitis. Expressed prostatic fluid contains more than 10 white blood cells per high-power field, indicating prostatitis.
Urine culture with greater than 100,000 colony-forming units (CFU) of Escherichia coli, the most common pathogen in acute and chronic prostatitis. Chronic bacterial prostatitis must be confirmed and diagnosed using a urine culture.
A nonspecific mixed inflammatory infiltrate that consists of lymphocytes, plasma cells, and histiocytes is typical in chronic bacterial prostatitis.
Bacterial prostatitis. Expressed prostatic fluid contains more than 10 white blood cells per high-power field, indicating prostatitis.
A nonspecific mixed inflammatory infiltrate that consists of lymphocytes, plasma cells, and histiocytes is typical in chronic bacterial prostatitis.
Urine culture with greater than 100,000 colony-forming units (CFU) of Escherichia coli, the most common pathogen in acute and chronic prostatitis. Chronic bacterial prostatitis must be confirmed and diagnosed using a urine culture.