Because of the focal nature of chronic bacterial prostatitis, needle biopsy of the prostate gland for culture of tissue is unreliable. Demonstration of leukocytes in prostatic fluid is not specific for bacterial prostatitis. There is a quantitative localization technique for making the bacteriologic diagnosis. Because bacteria present in the urethra can contaminate prostatic secretions obtained by prostatic massage, accurate diagnosis requires simultaneous quantitative cultures of urethral urine, midstream urine, prostatic secretions expressed by massage, and the urine voided after massage. An ejaculate is probably preferable to expressed secretions.

Specimens must be cultured immediately after collection, and methods of quantitating small numbers of bacteria must be used. The study should be done at a time the patient has no significant bacteriuria. If bacteriuria is present, ampicillin, cephalexin, or nitrofurantoin should be given for two to three days to sterilize the urine; these agents will not affect prostatic bacterial counts in chronic bacterial prostatitis. If chronic bacterial prostatitis is present, the number of bacteria in the expressed secretions or ejaculate will exceed those in urethral or midstream urine by at least 10-fold. If no secretions or ejaculate can be obtained, the bacterial counts in the postmassage specimen should be at least 10-fold higher than the urethral or midstream samples.

Chronic bacterial prostatitis is very difficult to cure because few antimicrobial agents penetrate the noninflamed prostate. Further, the nidus of infection in some patients may be small prostatic calculi that presumably are difficult to sterilize. Chronic bacterial prostatitis is therefore likely to persist and cause relapsing urinary tract infection. Unlike classical urinary tract infection, relapses may occur after long periods without bacteriuria (e.g., months). Transurethral prostatectomy is curative only if all the infected tissue is removed; about one third of patients will be cured by this procedure. Total prostatectomy is contraindicated because of the complications of sexual impotence and incontinence.

Until recently, medical therapy for patients who have chronic bacterial prostatitis consisted of treatment for bacteriuria followed by daily low dose suppressive antibacterial therapy. With these regimens, most patients remain relatively asymptomatic. However, the pathogen persists in the prostatic fluid cultures, and cessation of antibiotic therapy eventually results in relapse of urinary tract infection. Trimethoprim-sulfamethoxazole now appears to be the most effective therapy available for chronic bacterial prostatitis. Approximately one third of patients can be cured with prolonged therapy with this agent (i.e., two tablets given twice daily for 12 weeks). If this regimen fails, the patient should be managed either by treating acute exacerbations of urinary tract infection or by chronic suppressive therapy using low daily doses (e.g., half normal doses) of an antimicrobial agent.

Diseases of the Prostate Gland

Prostatitis

2. Chronic Prostatitis

Chemotherapy has given a new hope in the treatment of chronic prostatitis, with the introduction of the sulf onamides and mandelic acid. Other useful drugs are salol and methenamine used with acid sodium phosphate. When prostatic pain is very severe, sedatives are often necessary. The barbiturates usually suffice, but occasionally it is necessary to give codeine, pantopon, or morphine. When there is pain in the region of the prostate, or during micturition, the patient should be given a soothing prescription, such as Kirwin’s mixture:

Spices and alcohol should be eliminated from the diet and constipation avoided. When there is marked vesical irritation, a restricted diet should be used, which limits meat, tea and coffee, and eliminates certain foods which are irritating to the bladder, such as asparagus, carrots, tomatoes, berries.

The application of heat to the inflamed prostate has definite therapeutic value. Relief may often be obtained by hot sitz baths, hot rectal irrigations, diathermy, or radiothermy. The Elliott treatment regulator, introduced through the rectum, is an effective method of applying dry heat directly to the prostate and adjacent structures.

Occasionally a prostate becomes so infected that no amount of treatment by these methods will effect a cure. Total prostatectomy is then indicated.

Diseases of the Prostate Gland

Prostatitis

2. Chronic Prostatitis

To secure uncontaminated prostatic secretion the patient is first asked to void his urine; the penis and meatus are cleansed with green soap and water; and the anterior urethra irrigated with rivanol dextrose, acriflavine, or other antiseptic solution. The patient kneels on the table and a small endoscopic tube is inserted to a point beyond the external sphincter into the prostatic urethra. He then bends over and rests on his hands or elbows. The prostate is massaged firmly but gently and finally the prostatic urethra emptied by vigorous strokes down the middle depression of the prostate. The uncontaminated prostatic fluid is received in a sterile test-tube which the assistant holds at the end of the endoscope.

Normal prostatic fluid is opalescent and viscid, and microscopically is seen to consist of corpora amylacea, lecithin globules, columnar epithelia, and occasional hyaline globules. In chronic prostatitis, the prostatic secretion is less opalescent than the normal fluid, and the normal elements are replaced by pus cells and degenerated epithelial cells. The degree of infection is measured by the amount of pus in relation to the lecithin. In well-developed chronic prostatitis much of the lecithin content will be replaced by pus cells, often in clumps. As the condition improves, the pus cells diminish and the normal elements reappear. Bacteria may be present in great numbers.

Urethroscopic examination of the posterior urethra is advisable in cases where palpation of the prostate and vesicles, analysis of the voided urine, and microscopic examination of the secretions have proved inconclusive. The marked chronic inflammatory changes that may be revealed by such examination not infrequently are the only clue to a low-grade prostatitis and vesiculitis.

Prognosis. The patient suffering from long-standing prostatitis is not easily cured and it is advisable so to inform him at the outset of treatment. Relief of symptoms by some form of therapy, especially urethral dilatation, massage, rectal heat, and chemotherapy, is possible in most cases; but reversion to a normal prostatic fluid is more difficult to obtain and requires complete removal of infectious foci and restitution of prostatic drainage.

Treatment. In general, treatment consists of dilatation of the prostatic urethra, prostatic massage, urethrovesical irrigations and instillations, heat applied in the form of hot rectal irrigations, hot sitz baths, or diathermy, chemotherapy, and hyperpyrexia and vaccine therapy in selected cases.

The elimination of distant foci of infection, in the tonsils, teeth, sinuses, or colon, is of the greatest importance. In these cases, local measures are useful in relieving the symptoms, but are of little value in cure of the prostatitis, which is dependent upon removal of the primary focus.

The main problem in the treatment of chronic prostatitis is the restitution of free drainage, since retention favors infection. The most effective method of restoring the potency of prostatic and ejaculatory ducts is by a gradual, gentle, but thorough dilatation of the prostatic urethra to its maximal capacity. Urethral dilatation should precede massage of the partially or totally retentive gland since massage is beneficial only when drainage can take place through patent ducts. Active instrumentation is permissible in most cases at the time of the first consultation, the only clinical requirement being a clear first glass of urine. Dilatation is best carried out by means of sounds (passed upon a bladder partly filled with a mild antiseptic solution). Dilatation is carried on two or three times a week until the largest possible sound has been passed on at least three occasions and has remained tight, indicating that the maximal capacity of the urethra has been reached. The voided urine should be examined before each instrumentation, and treatment discontinued whenever the urine becomes cloudy. A mild urethritis may develop when the occluded ducts resume drainage and empty their infectious contents into the urethra. It may then be necessary to employ urinary antiseptics: sulfanilamide, mandelic acid, salol, or methenamine with acid sodium phosphate — their selection depending upon the nature of the infecting organism. Clinical proof of improved drainage can be obtained by a comparison of the amount and composition of the secretion before and after dilatation.

When satisfactory drainage of the diseased prostate has been restored, digital massage may be given once or twice a week upon a bladder partly filled with antiseptic solution. The aims of prostatic massage are: (1) the gentle expression of the accumulated secretion, (2) a stimulation of the contraction of smooth muscle fibers, and (3) the stretching and final removal of marginal adhesions. The technique, as well as the results obtained, vary widely with different operators. The patient may stand with the body bent forward, as over the back of a chair, or be placed in the Sims’ position, or he may rest upon his knees and elbows. The operator, with his gloved index finger in the rectum, exerts gentle pressure upon the lobes palpable from that position, using a downward stroking motion with the force directed toward the urethra, the object being to empty the prostatic acini of their purulent contents and to break up adhesions about the gland. Secretions later may be expressed from the ejaculatory ducts and the sinus pocularis by bringing the firmly pressing finger downward along the posterior urethra. Most patients with chronic prostatitis are benefited by intelligent application of prostatic massage; but too early, too vigorous, too frequent, or unduly prolonged massage may cause acute epididymitis or other unfavorable reactions. The degree of pressure is a matter of experience and is governed largely by the degree of inflammation present. As a rule, massage is carried out twice a week at first — the treatments tapering off, as the condition improves, until the patient is receiving massage once a week, then every ten days, semi-monthly, and finally once a month.

Hyperpyrexia and vaccines, serums, and injections of foreign proteins have a limited usefulness. Hyperpyrexia has been found highly beneficial in certain severe cases of gonorrhea and in the treatment of most gonococcal complications, but it is expensive, very uncomfortable, and attended with considerable risk. We have found vaccines very helpful in certain cases of arthritis where the infective focus was in the prostate, but in other cases their use has resulted in no appreciable benefit. Intraprostatic injections of antiseptic solutions have been recommended for recalcitrant pyogenic prostatitis; our experience has been that the benefits are not sufficient to offset the hazards of this method.

Diseases of the Prostate Gland

Prostatitis

2. Chronic Prostatitis

Symptoms. The signs and symptoms of chronic prostatitis vary greatly. The most frequent complaints are of pain, a urethral discharge, which may be profuse or merely the so-called “morning drop,” and some disturbance of sexual function, always accompanied by neurasthenia. The pain may be local or referred. Ordinarily, it is located in the perineum, and may be described by the patient simply as a “heaviness” in the rectum. With this type there is generally a history of the passage of prostatic fluid on defecation. The pain may be referred down the back or inner sides of the legs, or into the groins, penis, or sacrum; or it may simulate that produced by renal or ureteral stone. Frequent and painful urination, urgency, and difficulty are all common complaints, and result largely from involvement of the posterior urethra and bladder neck. If abscess occurs in the course of a chronic prostatitis, which is not uncommon with pyogenic infections, there is increased leukocytosis and pain, chills, and a rise in temperature.

Frequently the predominant symptoms are metastatic, with absence of local symptoms, so that the prostate is not suspected.

Diagnosis. The diagnosis of chronic prostatitis should be based on (1) rectal palpation, (2) repeated analyses of the voided urine, (3) microscopic examination of the prostatic secretion and ejaculate, and (4) urethroscopic examination of the posterior urethra and vesical neck. It is often wise to delay this last procedure until the most distressing symptoms have been allayed by treatment.

Rectal palpation, though of the greatest importance, is not of itself sufficient to establish the diagnosis of chronic prostatitis since, not infrequently, palpation of the chronically inflamed gland may reveal no gross changes, yet pus cells will be found in the prostatic strippings. Many a prostate that feels normal functions poorly and contains large amounts of pus and debris, and many microorganisms.

Often, however, careful rectal palpation will reveal changes in and about the gland. It will be hard and nodulated, and usually adhesions can be felt extending from its lateral borders to the seminal vesicles and adjacent pelvic tissues. Such a prostate is ordinarily, but not always, enlarged, and sometimes there are boggy spots between the areas of induration. Areas of normal gland are usually present.

Microscopic examination of the prostatic fluid, expressed by massage, is the only reliable method of demonstrating the presence of infection in the gland. Often the diagnosis must rest solely on microscopic evidence of pus in the expressed secretions. In treating a case of chronic prostatitis, frequent microscopic examinations of the unstained prostatic fluid should be made, as the conditions present in the gland can be ascertained in this way much more accurately than by palpation. Negative findings on one examination of prostatic secretion are, however, insufficient proof of the absence of prostatitis, since pus in some instances does not make its appearance until after the prostate has been massaged from two to five times. The secretion expressed from the first massage may be from normal portions of the gland, and two or more manipulations may be necessary to open a pathway into the urethra from a closed-off focus of infection. Massage for diagnostic purposes must, of course, be carried out firmly enough to express the secretions, but very gently and cautiously; otherwise, epididymitis may result. The prostatic fluid should be stained at least once to ascertain the presence or absence of bacteria, and their type. Bacteria are more readily identified on smear than in culture, but many of the more chronic cases fail to show bacteria either on smear or in culture.

Diseases of the Prostate Gland

Prostatitis

2. Chronic Prostatitis

Chronic inflammation of the prostate gland is a very common condition in adult males. In our series of 350 postmortem studies, a large number of the specimens showed evidence of inflammation of the prostate.

The chronically infected prostate is a common focus of infection, and urologists have repeatedly emphasized the importance of examining the gland and its secretion when searching for the source of obscure infectious conditions. We regard the prostate as second only to infected tonsils as a cause of arthritis. It may also be responsible for endocarditis, neuritis, iritis, and myositis.

Etiology and Bacteriology. Chronic prostatitis may result from any cause which congests the gland, such as long-standing infection, sexual abuse, or instrumental or other trauma. Other possible etiological factors are prostatic calculosis, stricture of the urethra, and certain vitamin deficiencies and endocrine dyscrasias.

Chronic prostatitis is most frequently the sequel to an acute infection, which may be caused by either the gonococcus or other organisms. The incidence of acute prostatitis as a complication of gonorrheal urethritis has been variously estimated at from 50 to 90 per cent; and untreated acute gonorrheal prostatitis, or incompletely treated posterior urethritis, is undoubtedly the most important factor in the production of chronic prostatitis. Only immediately after the acute inflammation has subsided is the gonococcus to be found in the prostatic strippings.

Chronic inflammations are by no means always due to the gonococcus, however. Non-specific infection is common, and may be a direct extension from the urethra; or blood-borne from a focus in the tonsils, teeth, or sinuses; or the aftermath of an acute systemic infection. The most common organisms demonstrated are the colon bacillus and the staphylococcus, streptococcus and their subforms.

Pathology. Microscopically, there are usually to be observed regions of inflammatory reaction in and about the acini, characterized by an increase of the polymorphonuclear cells, lymphocytes, and plasma cells, with marked proliferation of connective tissue. In other cases, the micro-pathological changes consist in circumscribed areas of round cell or polymorphonuclear cell infiltration. Minute abscesses are sometimes observed.

In a large percentage of cases, cystoscopic examination will show pathological changes in the region of the bladder neck, trigone, or posterior urethra. There is usually more or less involvement of the seminal vesicles, which may be soft and atrophic, or enlarged and indurated.

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.

Antibiotic therapy with appropriate agents, even in well documented infections, rarely proved successful in the past because the diffusion of most antibacterial drugs from plasma into prostatic fluid provided too low a concentration to be effective. Of many drugs tested for diffusion across the prostatic epithelium only the basic macrolides (erythromycin and oleandomycin) achieved significant concentrations in the prostatic fluid. These drugs are ineffective against the common gram-negative organisms cultured from prostatic fluid. Trimethoprim has been shown in both dogs and man to reach higher concentrations in the prostatic fluid than in serum at the normal pH of prostatic fluid. The concentrations attained in the diseased prostate may be lower, since in prostatitis the prostatic fluid pH may be elevated, but are probably still effective. When trimethoprim is combined with a sulfonamide, synergistic antibacterial activity results, with both a bactericidal effect and delayed emergence of resistant strains. Because of a similar half-life, sulfamethoxazole has been used in the combined drug. Sulfamethoxazole attains a concentration in the prostatic fluid that is only 10% of that in the serum, but this concentration is sufficient to bring about the synergistic effects of trimethoprim-sulfamethoxazole, which has a wide range of activity against both gram-negative and gram-positive organisms.

Trimethoprim-sulfamethoxazole has previously been shown to be effective in treating chronic prostatitis. The present study was a further clinical assessment of the usefulness of this combination in clinically diagnosed chronic prostatitis.

Methods and materials

The 40 subjects in this study were patients who satisfied the criteria of clinical diagnosis, who completed a 6-week course of trimethoprim-sulfamethoxazole (two tablets twice daily) and were available for review at 6 months or later. Clinical data on these patients are set forth in Table 2. All cultures of midstream urines and cultures for tubercle bacilli were negative. Serum acid phosphatase values were normal in all. Intravenous urograms were normal and no patient had a significant amount of residual urine. Those examined by cystourethroscopy showed only changes compatible with chronic prostatitis. None of the needle biopsies of the prostate was significantly abnormal.

Patients were reviewed 2 weeks after completion of treatment and again at 6 months or later. Routine bacteriologic examination of midstream urines, expressed prostatic fluid (when obtained) and postmassage urines was carried out.

Assessment was based on clinical signs and symptoms and the appraisal was made by one observer.

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.

ofloxacin

norfloxacin

ciprofloxacin

ampicillin

amoxicillin

gentamicin

tobramycin

U.S. Food and Drug Administration:

Active Ingredients: Sulfamethoxazole and Trimethoprim
Drug Name: Bactrim, Cotrim, Polytrim, Septra, Sulfamethoprim, Sulfatrim, Sulmeprim, Uroplus

Active Ingredients: Trimethoprim
Drug Name: Primsol, Proloprim, Trimethoprim, Trimpex

Active Ingredients: Sulfamethoxazole
Drug Name: Gantanol, Sulfamethoxazole, Urobak

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.