Results

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.

Treatment

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.

Chronic prostatitis is a common condition occurring in younger men which presents problems of diagnosis and treatment. In some patients a bacterial population of known pathogens can be identified in the prostatic fluid. In many others proof of bacterial etiology is lacking. There has therefore been an acceptance of two common forms of the disease, namely chronic bacterial prostatitis and a condition that has been variously termed chronic abacterial prostatitis, nonspecific prostatitis, prostatosis and prostatic neurosis. Despite the refinements of methods of collection and bacteriologic processing of prostatic fluid, certainty of bacterial recovery cannot be assumed. The sample obtained may fail to include fluid from all parts of the gland or, in particular, from the inflamed parts of the gland. The inconsistency of recovery of bacteria from known cases of bacterial prostatitis lends support to this thesis and suggests that the segregation of chronic prostatitis into bacterial and nonbacterial groups is by no means certain. Where episodes of recurrent genitourinary infection such as cystitis, epididymitis and, less commonly, pyelonephritis occur, bacterial etiology is more likely to be established but otherwise the distinction between differing clinical entities is not obvious.

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.