Nonbacterial prostatitis (NBP) is the most common type of prostatitis, and occurs eight times more frequently than bacterial prostatitis. Nonbacterial prostatitis presents with the same signs and symptoms as bacterial prostatitis; however, prostatic fluid cultures are negative for presence of bacteria. Inflammation is evident upon prostatic fluid analysis, and can be identified by a minimum of 10 to 15 white blood cells per high power field on microscopic examination. Although controversial, implicated pathogens include Chlamydia trachomatis, Ureaplasma urealyticum, and Trichomonas vaginalis. Minocycline 100 mg twice daily, doxycycline 100 mg twice daily, or erythromycin 500 mg four times daily have been utilized in order to eradicate the suspected pathogens. Erythromycin’s antimicrobial activity is significantly enhanced in the presence of the alkaline pH in prostatic fluid, thus, it achieves high cure rates of prostatic infections. Treatment duration is approximately 2 to 4 weeks. Prolonged therapy after treatment failure is not indicated, since nonbacterial prostatitis is generally self-limiting. Adjunctive recommendations may include sitz baths, normal sexual activity, and analgesics for painful urinary symptoms.

Spicy foods, caffeine, and alcohol should be avoided; they may cause bladder irritation and spasms culminating in reflux of urine into prostatic ducts, thus exacerbating nonbacterial prostatitis symptoms. If symptomatology persists patients should be referred to a urologist for evaluation of serious conditions such as urinary bladder carcinoma and interstitial cystitis.

Conclusion

As the most accessible health care professional, the pharmacist often encounters patients with prostatitis. Treatment of prostatitis is associated with high failure rates; therefore it is paramount that pharmacists counsel patients regarding prostatitis and its treatment. Since prostatitis tends to require prolonged therapy, patients must understand the importance of compliance. Pharmacists must carefully screen for drug interactions that may decrease compliance and efficacy. Furthermore, pharmacists play a vital role in referring patients who are unresponsive to therapy for evaluation of serious underlying conditions.

Diagnostic events (in squares) in the sequence of  screening and follow-up for prostate cancer. The size and darkness of the curved arrows indicate the current knowledge regarding diagnostic tools. Block arrows indicate the function of diagnostic modalities regarding the outcome of events.

Private Parts. An Owner's Guide to the Male Anatomy, 2nd Ed

Yosh Taguchi

McClelland & Stewart Inc, Suite 900, 481 University Ave, Toronto, ON M5G 2E9
1996/320 pp

Strengths

Easy to read, no-nonsense language, mostly accurate information

Weaknesses

Not always strongly evidence-based, sometimes too much emphasis on surgery, not patient-centred

This is Dr Taguchi’s second and updated edition of his “Canadian bestseller” first published in 1988. He is a well-known Montreal urologist who says he wrote this as “… the answer to all those questions I have ever been asked… in my office.” Further, as it says on the jacket, “Most men know more about their cars than about the workings of their own bodies.” Many family physicians would agree.

This book is a cleanly laid out, how-to manual for men who want to know more about their genitourinary system. The first chapter deals with basic anatomy and functions. The rest covers various problem areas, such as impotence (when will the medical establishment call this erectile dysfunction?), infertility, vasectomy, lumps, prostate problems, sexually transmitted diseases, and incontinence. The information is straightforward and accurate, and the last few pages contain commonly asked questions and answers.

The section on prostate problems is full of details on diagnosis and management. The author, however, gives too much information on surgical aspects, walking readers through every detail of how he performs the surgery. I also objected to the way routine prostate-specific antigen screenings and almost routine surgery (for prostate cancer) were encouraged. The evidence is still unclear about whether routine prostate-specific antigen screenings help, and no one will pass the College of Family Physicians of Canada’s (CFPC) examination if they push surgery for prostate cancer. I also believe the author makes too light of the quite high postoperative rates of erectile dysfunction. I have fewer points to criticize in the other sections. The details on STDs are good, and I liked the case reports in the section on lumps. This book might not pass the CFPC’s standard for patient-centred material; however, I recommend it as a practical book for patients and residents as long as their physicians read it first.

The leading test to detect prostate cancer is “clinically useless” at determining the size or severity of a man’s tumor, and is only of “limited” value at predicting cure rates from surgery to remove the diseased gland, a new study says.

The test, which measures a blood enzyme called prostate-specific antigen (PSA), is likelier to find benignly enlarged prostates and prompt overly aggressive treatment, according to the scientists who conducted the study.

The study, which appears in the January issue of the Journal of Urology, “is quite a disappointment,” says Dr. John McNeal, a Stanford University pathologist and a co-author of the paper.

“We used to think [PSA testing] was good. But what we would like it to tell us is whether a PSA that is not much elevated is elevated because of [normal prostate growth] or whether it’s elevated because of prostate cancer.” And the protein, at least at moderate levels, can’t do that, McNeal says.

Dr. Peter Albertsen, chief of urology at the University of Connecticut in Farmington, says the study “is not going to knock prostate-specific antigen (PSA) screening off the map by any means.”

However, Albertsen adds, PSA testing is undergoing a crisis of confidence similar to that of screening mammography, another exam whose value has come under questioning.

“I think there’s enough tantalizing evidence to think” that routine prostate-specific antigen (PSA) screening saves lives, Albertsen adds. But there’s not enough evidence to be sure.

Almost 190,000 American men are diagnosed annually with prostate cancer, and 30,000 will die from it, according to the American Cancer Society. Prostate-specific antigen (PSA) testing is widespread in men over age 50, but no study has proved that it saves lives by helping doctors identify prostate tumors when they’re still curable.

One reason: prostate cancer grows glacially. So while most men will die with cancer of the gland, relatively few will die of it. Aggressive treatment of slowly growing tumors may therefore cause more harm than good, some experts argue.

In the latest study, Dr. Thomas Stamey, a Stanford University urologist, and his colleagues studied the relationship between PSA scores in 875 men who underwent radical prostate surgery, in which the gland was completely removed, between 1984 and 1997.

Stamey’s group analyzed prostate-specific antigen (PSA) readings taken from many of the men both before and after their operation.

The largest tumors did produce extremely elevated PSA levels, topping 22 nanograms per milliliter of blood. Scores of more than 9 ng/ml were somewhat associated with aggressive disease, as measured by standard gauges of malignancy.

But for prostate-specific antigen (PSA) values between 2 and 9 ng/ml, the culprit was often not cancer but benign prostatic hypertrophy (BPH), or normal swelling of the gland.

Nor did PSA testing predict cure rates: Surgery success was the same for men whose pre-operation PSA was lower than 4 ng/ml as it was for those with a score of 10 ng/ml.

The prostate-specific antigen (PSA) enzyme is secreted by cells in the prostate, and mildly elevated values often reflect a larger than normal gland. BPH is as common as cancer, a fact many men don’t realize.

Scientists have been trying to tweak the prostate-specific antigen (PSA) test to make it more reliable, but whether these new techniques will be more sensitive to cancers remains a mystery. In fact, PSA is a misnomer, since the enzyme is secreted not only in the prostate but in the breast as well.

What To Do

Every man has a prostate-specific antigen (PSA) level, and any score between one and four could be totally normal, McNeal says. The tricky part comes in deciding what to do if the test comes back between 7 and 8. Despite his group’s findings, McNeal says he would probably undergo a biopsy if his own PSA test were in that range.

The clinician will usually press on and manipulate (palpate) the abdomen and flanks to detect signs of kidney or bladder abnormalities. The clinician will also check for signs of anemia or swelling in the legs and arms. Certain procedures that test reflexes, sensations, and motor response may be performed in the lower extremities to rule out possible neurologic causes of bladder dysfunction.

To determine whether the bladder is obstructed, a uroflowmeter is employed to determine the speed of urine flow. This device does not determine the cause of obstruction but only that obstruction exists. Since numerous factors can affect urine flow (including straining or holding back because of self-consciousness) this test should be conducted more than once to ensure accuracy and reliability. The rate of urine flow is calculated as milliliters of urine passed per second. The flow of urine normally decreases as men get older, ranging from more than 25 mL/second in young men to less than 10 mL/second in elderly men. Men with peak flow rates less than 12 mL/second are more likely to suffer from urinary retention.

Urinalysis is utilized to detect signs of bleeding, infection, or bladder cancer. Urinary infections are more common in older men, particularly those with benign prostatic hyperplasia. A Pre and Post Massage Test (PPMT) of the prostate is about 90% accurate in ruling out prostatitis.

A PSA (prostate specific antigen) test is the standard screening device for detecting prostate cancer but is often used in men with suspected BPH. It is recommended annually for all men over 50 years old and for men over 40 who are at high risk for prostate cancer. The value of the test in a man over 70 with benign prostatic hyperplasia is questionable, since BPH itself can raise PSA levels. The test measures the amount of prostate specific antigen in the blood. A PSA of 4 ng/mL or lower is considered normal whereas a level of 5 to 10 ng/mL is considered to be slightly elevated. A prostate specific antigen reading above 10 ng/mL is considered to be moderately to highly elevated. It should be noted that most men with slightly elevated PSA levels do not have prostate cancer, but that a normal prostate specific antigen level does not rule out the presence of cancer. Therefore, a biopsy is often performed to rule out prostate cancer. Prostate specific antigen levels tend to increase with age. A PSA level of 2.5 ng/mL is considered to be normal in men age 40 to 49, whereas a level of 3.5 ng/mL is considered to be normal in men age 50 to 59. It is not uncommon to routinely see prostate specific antigen levels of 6.5 ng/mL or higher in men age 70 and older. A more recent test identifies free PSA, which is found in lower levels when prostate cancer is present and in higher levels with benign prostate hyperplasia. Certain treatments for BPH, including finasteride or transurethral resection of the prostate (TURP), may reduce prostate specific antigen levels and possibly mask existing cancer.

A postvoid residual urine (PVR) test measures the amount of urine left in the bladder after urination. A PVR reading of less than 50 mL generally indicates adequate bladder emptying. Excessive residual urine (100 to 200 mL or higher) may indicate the presence of a neurologic disease that is impairing bladder function.

Ultrasound of the prostate is a noninvasive approach toward an accurate account of the size and shape of the prostate. Ultrasound tests can be administered via a rectal probe (transrectal ultrasonography) or abdominal sensor (transabdominal ultrasonography). Transabdominal ultrasonography offers a more accurate measure of postvoiding and residual urine, and is less invasive and expensive than transrectal ultrasonography. However, transrectal ultrasonography is significantly more accurate in determining prostate volume and can detect cancer.

Filling cystometry is useful in patients who cannot urinate and in whom nerve damage or injury of the bladder is suspected. The test is used to determine the absence or presence of uninhibited detrusor contractions (UDC), which often occur in men with storage urinary tract symptoms. During this procedure, sterile water is instilled into the bladder and the pressure in the bladder is continuously measured until the patient feels the need to void. Then a fluid-inflatable balloon is inserted into the rectum for a second measurement that reflects abdominal pressure, which is calculated together with the measurements of bladder pressure to provide an accurate assessment of detrusor contractions.

Urethrocystoscopy is particularly useful in men with suspected urinary tract complications, as noted from blood in the urine, infection, bladder cancer, or prior surgery or injury. This procedure can confirm the diagnosis of benign prostatic hyperplasia. Possible complications associated with this procedure include hypersensitivity reactions to the local anesthetic, urinary tract infection, bleeding, and urine retention. An intravenous pyelogram (IVP), which utilizes an injected dye to detect urine flow on roentgenogram, is also useful for determining urinary tract infections or complications.

Of the 40 patients who received trimethoprim-sulfamethoxazole for 6 weeks, 9 were classed as failures. These either had no response or relapsed during therapy or relapsed after therapy with unchanged severity of symptoms.

Eleven were considered improved on the basis of continued symptomatic improvement or because of a good initial response followed by relapse with symptoms less severe than before treatment. Included in the “improved” group are two patients who initially relapsed but who have since remained asymptomatic on long-term therapy.

The 20 patients who have had continued satisfactory relief of symptoms are classified as having good results.

Discussion

An earlier controlled study compared the results of treatment with sulfamethoxazole with those from the use of trimethoprim-sulfamethoxazole. Only after 6 weeks of treatment was a significant response obtained and this influenced the choice of 6 weeks as the treatment period. A longer period of treatment (12 weeks) produced better results when trimethoprim-sulfamethoxazole (TMP-SMX) was used after a course of sulfamethoxazole. The late results, however, showed no significant differences according to the sequence in which the agents were given. In this later survey a similar success rate was obtained, namely 50% in patients with the clinical manifestations of chronic prostatitis.

When we disregarded bacterial counts of less than 3000/ml, which is standard practice, only one of the patients was reported as having a growth of Escherichia coli. This is in contrast with the earlier report, in which meticulous bacteriologic investigation, including use of anaerobic culture, showed that 66% of patients had pathogens in their prostatic fluid.

It is concluded from our results in this small series that there is justification for use of trimethoprim-sulfamethoxazole in patients with chronic prostatitis where proof of bacterial etiology is lacking. The desirability of meticulous bacteriologic studies is not disputed.

Diagnosis

The common clinical features of chronic prostatitis are summarized in Table 1. A variety of complaints, singly or in various combinations, may be elicited, the most common being urinary symptoms and discomfort and pain in various sites. Less common symptoms include hemospermia, perineal discomfort or pain after ejaculation. Others relating to sexual function are sometimes emphasized but are probably coincidental. There is considerable variation between patients in severity of symptoms but the clinical pattern appears to be consistent for individual patients.

Changes are commonly detectable on rectal examination of the prostate although normal palpatory findings may be encountered. These changes include variations in:

(1) size;

(2) consistence, such as areas of softening or bogginess with or without areas of induration;

(3) contour, with irregularity of the surface; and

(4) amount of discomfort or pain on palpation.

Assessment of these changes lacks the precision of bacteriologic quantitation but, provided the limitations are recognized, may still be valuable in diagnosis and assessment of therapy in chronic prostatitis.

The number of pus cells in prostatic fluid shows such variation from day to day in individual patients, unrelated to clinical course, that this feature lacks value in diagnosis or review.

Cystourethroscopy may show typical changes in the prostatic urethra but the importance of these has been largely discounted because to a minor degree they may be seen in asymptomatic patients. Apart from illustrating some typical prostatic changes, this examination is useful in excluding other pathologic conditions of the prostate and bladder. Trabeculation of the bladder in young men with prostatitis is seen frequently enough to suggest a relationship with dysfunctional voiding.

Radiologic studies including intravenous urograms serve to exclude other causes of urinary tract infection. Prostatic calculi may be demonstrated.

Needle biopsy of the prostate has been generally unrewarding either in demonstrating pathological changes or in isolating bacteria.

Bacteriologic diagnosis in chronic prostatitis was considerably advanced by the refined techniques introduced by Meares and Stamey. Their studies indicated the value of taking samples of urine from the first voided specimen (VB1), from a midstream specimen (VB2) and a voided specimen immediately after prostatic massage (VB3). Prostatic massage usually produces a specimen of prostatic fluid (EPS) for bacteriologic examination. Localization of the source of the infection may therefore be possible, although it must be remembered that all urine sampled passes through the prostatic urethra. In using these methods very sensitive bacteriologic culture techniques must be used to ensure counting of as few as 10 organisms per ml, because in chronic prostatitis there are often only small numbers of bacteria in the prostatic secretion (EPS) or urine after massage (VB3). This is the reason that routine bacteriologic studies of prostatic fluid or postmassage urine rarely show positive results.

Etiologic factors in chronic prostatitis are rarely obvious but include urethral stricture, previous urethritis (gonococcal or nonspecific), previous instrumentation or catheterization and previous episodes of acute prostatitis.

Chronic bacterial prostatitis (CBP) occurs when acute bacterial prostatitis is treated inadequately due to resistance, relapse, short-course therapy or because the ductal anatomy of the peripheral zone of the prostate may have blocked drainage of secretions from the prostate. Rarely will some patients be found who have not had a previous bout of acute prostatitis. The most common clinical feature of chronic bacterial prostatitis is recurrent urinary tract infections. Subsequently, patients will complain of obstructive and irritative urinary symptoms. Physical exam reveals a palpable, tender prostate. However, patients often present asymptomatic, with a normal prostate gland exam.

Localizing bacteria from the prostate is paramount in order to diagnose chronic bacterial prostatitis. The Stamy–Meares test is a collection of segmented urine samples from the urethra, bladder, and prostate; it is considered the gold standard for diagnosis. The patient voids and collects the first 5–10 mL of urinary stream (VB₁), then collects a midstream specimen of 10–20 mL (VB₂), and is administered a prostate exam and massage to express prostatic fluid (EPS). This is immediately followed by collection of a final urinary specimen with the first 10 mL of urine (VB₃). The specimens are then analyzed for bacteria and leukocyte count. In CBP, large numbers of leukocytes are present in the EPS and VB₃. However, these results have to be correlated with VB₁ and VB₂ results, since an active urinary tract infection will cause variable results.

The Gram-negative pathogens implicated in acute bacterial prostatitis have also been implicated in chronic bacterial prostatitis. Most clinicians discount Gram-positive bacteria as causative pathogens in chronic bacterial prostatitis. Fluoroquinolones and TMP/SMX are first- and second-line therapy in the management of chronic bacterial prostatitis, respectively. Other antimicrobials include doxycycline, minocycline, carbenicillin indanyl sodium, and erythromycin; however, these agents have shown variable results. Chronic prostatitis warrants at least 10 to 12 weeks of therapy. Usually, the bacteria remain susceptible to commonly used antimicrobials despite frequent, long-term use. However, poor clinical outcomes have been observed due to poor diffusion of antimicrobials into the prostate. As a result, long-term suppressive therapy may be needed. Long-term suppressive therapy may be initiated with TMP–SMX given as a single-strength tablet daily, trimethoprim 100 mg daily, sulfamethoxazole 500 mg daily, norfloxacin 200 mg daily, or nitrofurantoin 100 mg daily. Surgery may be an alternative in recurrent cases that are caused by infected calculi.

Acute bacterial prostatitis (ABP) is the least common of the prostate infections. It is usually accompanied by a urinary tract infection with positive cultures from prostatic secretions. It presents with a sudden onset of fever, chills, and low back and perianal pain. Patients often complain of obstructive (dysuria, nocturia, urgency, frequency, and burning) and irritative (hesitancy, straining, dribbling, weak stream, and incomplete emptying) urinary symptoms. Other constitutional symptoms include generalized malaise, arthralgias and myalgias. Physical examination reveals a warm, tender, swollen and indurated prostate.

The diagnosis of acute bacterial prostatitis can be made based on clinical signs and symptoms. Often, urinary cultures are positive and reveal Escherichia coli as the most prevalent pathogen. Other Gram-negative microorganisms from the Enterobacteriaceae class, such as Proteus sp. and Klebsiella sp., may also be present. In patients who present with a recent history of hospitalization and/or broad-spectrum antimicrobial use, a high index of suspicion for Pseudomonal, Enterococcal and Staphylococcal infections should be maintained.Other microorganisms implicated in prostatitis include Ureaplasma urealyticum, Chlamydia trachomatis, and Corynebacterium seminale. Occasionally, urinary cultures will be negative. Bacteria may be isolated from prostatic fluid by prostatic massage, although it is not recommended since vigorous manipulations can lead to bacteremia.

The mainstay of therapy in acute bacterial prostatitis is empiric antimicrobial therapy directed toward the most likely pathogens. Urinary cultures should be obtained prior to initiating antimicrobial therapy to allow for identification of the causative pathogen and subsequent streamlining of pharmacotherapy. Generally, antimicrobials penetrate poorly into the prostate gland due to the lipid solubility and pH of the prostate epithelial membrane. However, since inflammation is invariably present in acute prostatitis, most antimicrobials will readily diffuse into the prostate gland.

The most commonly prescribed antimicrobial for acute bacterial prostatitis is trimethoprim/sulfamethoxazole (TMP–SMX) due to its broad-spectrum activity against the most prevalent isolated pathogens. Trimethoprim inhibits bacterial dihydrofolate reductase; it works synergistically with sulfamethoxazole to interfere with microbial folic acid synthesis. Trimethoprim concentrations in prostatic fluid are two to three times that in serum, thus achieving adequate concentrations at the site of infection. The usual dose is 160 mg of trimethoprim and 800 mg of sulfamethoxazole, which is equivalent to one double-strength tablet (e.g., Septra DS, Bactrim DS) taken twice a day. TMP-SMX has a good safety profile, with most of the adverse effects limited to hypersensitivity reactions and gastrointestinal disturbances including nausea, vomiting, diarrhea, and anorexia. Other, more serious adverse effects such as leukopenia, thrombocytopenia and granulocytopenia are uncommon (they are prevalent, however, in the AIDS population).

The fluoroquinolones have gained popularity in the management of acute bacterial prostatitis due to their enhanced activity against many of the Gram-negative pathogens in urinary tract infections. The fluoroquinolones inhibit bacterial replication and transcription by blocking bacterial DNA gyrase and subsequent protein synthesis. Prostatic fluid contains lower fluoroquinolone concentrations than does serum; nevertheless, appreciable concentrations are achieved in prostatic tissues to eradicate the most common causative pathogens. Ciprofloxacin, ofloxacin, and norfloxacin are effective fluoroquinolones in the management of prostatitis; however, only ofloxacin and norfloxacin are FDA-approved. Adverse effects associated with the fluoroquinolones include nausea, vomiting and diarrhea; dizziness, lightheadedness, confusion, insomnia, hallucinations; tendonitis and tendon rupture; and photosensitivity reactions. Rash that may progress to an anaphylactoid reaction has occasionally been reported. Recent data have demonstrated higher eradication rates for the parenteral administration of fluoroquinolones (67%–91%) than for TMP–SMX (40%–71%); however, clinical efficacy with oral therapy in outpatients has been similar.

Rarely, patients who present acutely ill will require hospitalization with intravenous therapy (e.g., those who present with bacteremia or significant voiding difficulties). Generally an aminoglycoside in combination with ampicillin or parenteral TMP–SMX is initiated. The penicillins inhibit cell wall synthesis, and the aminoglycosides bind to bacterial ribosomes, inhibiting protein synthesis. The aminoglycosides and penicillins often yield a synergistic bactericidal effect. Patients requiring initial intravenous therapy should be switched based on culture and sensitivity reports to an oral antimicrobial once acute symptoms have resolved.

The duration of treatment for acute bacterial prostatitis is uncertain; however, most authorities suggest 4–6 weeks of therapy. Short-course therapy is not recommended due to the risk of relapse or progression to chronic bacterial prostatitis.

Prostatitis is a broad term used to identify perianal and lower urinary tract symptoms in men. Prostatitis rarely occurs in males less than 30 years of age; however, it is a common problem in older males. Epidemiological data reveal that up to 50% of all males will develop an episode of prostatitis. Disorders involving inflammation of the prostate gland and its surrounding tissue may be classified into three distinct types: acute bacterial prostatitis, chronic bacterial prostatitis and nonbacterial prostatitis. Since the prostate is a privileged site (an area in which antimicrobial penetration is generally poor), the efficacy of antimicrobial agents is limited, a long duration of treatment is required, and failure rates are high (30%–40%). Furthermore, the diagnosis of prostatitis is both nebulous and controversial. As a result, the diagnosis and therapy of prostatitis remains a challenge. In this review we will discuss the pathophysiology, diagnosis and treatment of bacterial and nonbacterial prostatitis.

Pathophysiology of Prostatitis

Various physiological factors contribute to the development of prostatitis. Prostatic antibacterial factor (PAF) is a bactericidal fluid secreted from the normal prostate. Prostatic antibacterial factors antibacterial activity is dependent on adequate prostatic zinc concentrations. Both PAF and PAF zinc concentrations are diminished in patients with prostatitis. Normal prostatic secretions generally maintain a pH of approximately 6.6 to 7.6. With increasing age, the pH of prostatic secretions tends to rise. Patients with prostatitis have alkaline prostatic secretions ranging in pH from 7–9. Whether these physiological factors are a cause or effect of prostatitis is unknown. The introduction of bacteria into the prostate is multifactorial and includes an ascending urethral infection, reflux of infected urine into prostatic ducts which empty into the posterior urethra, invasion of rectal bacteria by direct extension into the prostate or by lymphatic spread, and hematogenous spread. It is postulated that intraprostatic urinary reflux, either with infected urine or sterile urine, may be the primary etiology of most bacterial and nonbacterial prostatitis cases.