Prostatitis an increasing clinical problem for diagnosis and management

Transcription

1 Journal of Antimicrobial Chemotherapy (993) 32, Suppl. A, -9 Prostatitis an increasing clinical problem for diagsis and management D. A. Leigh Department of Microbiology, Wycombe General Hospital, High Wycombe, Bucks HP 2TT, UK Prostatitis remains a challenging condition. The clinical features are often nspecific while the aetiology and pathogenesis can be diverse and includes inflammatory, obstructive, and/or chemical causes and may also be related to calculi. Four categories are recognized: acute bacterial prostatitis, chronic bacterial prostatitis, n-bacterial prostatitis and prostatodynia. The diagsis of prostatitis was advanced substantially by the introduction of sequential sampling of urine aliquots following prostatic massage. Bacterial prostatitis is largely associated with the Enterobacteriaceae although Pseudomonas spp., enterococci and Staphylococcus aureus may also be isolated. In chronic bacterial prostatitis a variety of streptococci and anaerobic bacteria may be isolated. Treatment is difficult largely owing to the limited range of agents able to achieve therapeutic concentrations within prostatic fluid, which has a ph lower than that of plasma. Trimethroprim, co-trimoxazole and the tetracyclines have been widely used. The quilones have recently been shown to diffuse readily into the prostate; ofloxacin and temafloxacin have produced the highest concentrations in prostatic fluid. Antibiotic treatment requires prolonged high dosage and careful monitoring to ensure that bacterial eradication has occurred. Other forms of management have included the judicious use of antiinflammatory agents and analgesics. In some patients zinc sulphate has proved to be of symptomatic benefit. Introduction Prostatitis is a difficult and puzzling syndrome. Whilst it rarely affects the younger male adult it appears to be common in men aged 30 years or more. It may present with a wide variety of symptoms which do t necessarily primarily involve the urinary tract and may be pelvic, testicular, or genital. The clinical findings may be n-specific and comparison of various published studies can be difficult to interpret. It is recognized that there are several distinct forms of the syndrome and the success of treatment depends on a specific diagsis. The aetiology may be infective, inflammatory, obstructive, physiologically deficient or chemical, and calculi may be formed. The incidence of prostatitis is t well understood in the UK although it commonly presents to general practitioners. In the USA 25% of visits for men with genitourinary symptoms are due to prostatitis (Lipsky, 989) and 50% of men will suffer from prostatitis during their life (Stewart, 988). Men presenting with symptoms of a urinary tract infection may have associated bacterial prostatitis which may subsequently recur following treatment causing symptoms. A major difficulty with prostatitis is that a high level of investigation is necessary to make the diagsis and this needs reference to a specific service. O3O5-7453/93/32AOO +09 $08.00/0 993 The British Society for Antimicrobial Chemotherapy

2 D. A. Leigh TaWe I. Clinical features of prostatitis syndrome (cf. Meares (99)) Syndrome Confirmed UTI Prostate examination Prostatic WBC fluid culture Response to antimicrobial therapy Impaired urinary flow ABP CBP NBP PD usually rmal varied varied usually rmal but slow poor ± + ABP, Acute bacterial prostatitis; CBP, chronic bacterial prostatitis; NBP, n-bactenal prostatitis; PD, prostatodynia. Types of prostatitis The classification of the most common types of prostatitis was introduced in 978 (Drach et ai, 978), and four types are w recognized on the basis of bacterial culture of selective urine collections and prostatic fluid and microbiological examination of the prostatic fluid. The four categories are; acute bacterial prostatitis (ABP), chronic bacterial prostatitis (CPB), n-bacterial prostatitis (NBP), and prostatodynia (PD). Many features of these four syndromes are similar but each syndrome has certain individual characteristics (Table I). Acute prostatitis is usually easy to diagse as it is a severe illness with fever, often rigors and lower back and perineal pain. Rectal examination of the prostate is usually very painful and massage is t recommended as bacteraemia may follow. The prostate is usually swollen, tense, with a smooth texture and may be warm to the touch. It is usually accompanied by bacteriuria and culture of the urine will identify the pathogen. Chronic bacterial prostatitis is usually a relapsing infection with varying clinical symptoms which may occasionally be acute. It is usually accompanied by a history of recurrent UTI and the symptoms are due to the pathogen persisting in the prostatic tissue despite treatment. Most men complain of pain or discomfort in the perineum, groin, low back or scrotum and may have voiding dysfunction. Frequency and cturia may be present but dysuria is very variable. Prostate examination is usually t very helpful as many different features are found. Non-bacterial prostatitis is an inflammatory condition where all bacteriological studies are negative. It does t have a history of preceding UTI but symptoms may be similar to chronic bacterial prostatitis. In some cases the prostate is very boggy with dular areas and massage will result in increased prostatic fluid collection which shows large number of WBC and macrophages. In others the prostate is fibrous and massage is difficult. In many instances the inflammation may be chemical in origin due to interprostatic reflux of urine. Prostatodynia is a condition where the patient has symptoms referrable to the prostate but with abrmality in the prostate, prostatic fluid or evidence of infection. It may be associated with stress, emotional tension or sexual difficulties and there may be bladder neck or urethral spasm (Meares, 99). The typical man with prostatodynia has symptoms of abrmal urinary flow, and a wide variety of pain or discomfort in the perineum, groin, testicles and particularly the penis and urethra. Examination of certain clinical and laboratory features of the four syndromes can help to differentiate between them although there is considerable overlap (Table I).

3 Prostatitis: diagsis and management Table II. Procedure of Stamey test. No antibiotic for seven days or more 2. In uncircumcised men examine the glans penis; if discharge present take swab 3. In all men clean glans penis with sterile water and dry before collecting urines and 2 4. Maintain retraction of foreskin throughout test 5. Collect first 5-0 ml urine passed (. Urethral urine) 6. Continue passing urine in to toilet for up to 2-5 sec 7. Collect 0-20 ml urine (2. Bladder urine) 8. Carry out prostate examination and massage for min with a container over the glans penis 9. Collect prostatic fluid directly into container during massage and by gentle penile massage afterwards 0. Clean glans penis with sterile water and dry. Collect first 5-0 ml urine passed (3. Prostatic urine) The incidence of the four forms of prostatitis is t well kwn but bacterial prostatitis is relatively uncommon. It is probable that 50-60% have n-bacterial prostatitis, 30% have prostatodynia and 5-0% have acute and chronic bacterial prostatitis (Brunner et al., 983). Investigation of prostatitis Although bacterial prostatitis is uncommon it is easier to treat and so all men with symptoms referrable to the prostate should have bacteriological investigations. Acute bacterial prostatitis is usually easily diagsed by urine culture as there will be heavy overflow of prostatic fluid and pathogens into the urine. It is important in chronic conditions that the men should undergo a Stamey urine technique (Meares & Stamey, 968), and have microscopical and cultural examination of the prostatic fluid and seminal fluid. Stamey test Patients must be properly prepared for this test, which depends on the collection of specific sequential specimens of urine as shown in Table II and the Figure. It is important that the patient should have a well filled but t over distended bladder. It is t easy to collect specific portions of urine with an overfull bladder as control of I Urethral Z Bladder 3 Prostotic In all men clean penis _ with water and dry 3 sec later ml Prostate examination and massage I si voided (5mL) MSU (0-20 ml) Prostatic Fluid Figure. Details of the Stamey-Meares test. st voided (5mL)

4 4 D. A. Leigh control of passage of urine may be difficult. The preparation of the glans penis is important in both uncircumcised and circumcised men and a glans swab before the test will show the bacterial colonization in this area. If full retraction of the foreskin does t occur throughout the test, the glans penis should be cleaned and dried before each urine sample is collected. The volume of the three urine samples is important. The urethral specimen should be small (5-0 ml) but the midstream specimen (bladder) may be any volume. Prostatic massage may be difficult. With a rmal prostate this maeuvre may cause considerable discomfort and in acute bacterial prostatitis and sometimes chronic bacterial prostatitis massage may be very painful and prevent collection of a significant volume of prostatic fluid. It is likely however, that secretions will have been expressed into the prostatic urethra and the post-massage urine may contain obvious fluid. It is important that the third urine sample be as small as possible (5 ml or less). Culture of all specimens should be carried out immediately to avoid any effect of the urine on the prostatic fluid in a mixed third specimen. Culture of the urine should be a surface viable count dilution of 0"', and include agar plates and incubation for fastidious bacteria and anaerobic bacteria. The rmal range of agar plates are blood and MacConkey incubated aerobically, chocolate under CO 2 and blood anaerobically. The prostatic fluid should be cultured directly on to similar agar plates, and incubated for 48 h. Quantitative microscopy and biochemical examination of the urine and prostatic fluid should be carried out. The WBC count is important in reaching a diagsis and analysis of ph, specific gravity and protein may help. A Gram film of urine deposit and prostatic fluid will confirm the WBC count and show bacteria. Results of the Stamey test There are many combinations of results that can be found (Table III and IV). A typical bacterial prostatitis will show pathogenic bacteria in the third urine and prostatic fluid, and usually the count should exceed by ten-fold the counts in the first two urine specimens. (Table III A.) If all three urines show a high count of 0 5 organisms per ml then cystitis is present. In a specialized prostatitis clinic pre-stamey test bladder urines should be examined to exclude current cystitis, as this may prevent the accurate diagsis of bacterial prostatitis. However, even in the presence of cystitis an accompanying prostatitis may be suggested by a very high WBC count in the prostatic fluid. (Table IIIB). High counts of pathogenic bacteria in the urethral sample may be due to urethral infection, but may also represent pre-test discharges of prostatic bacteria into the urethra (Table FVA). In this case it is rmal to find a higher WBC count in the prostatic fluid than urethral urine. Urethritis may be present but in these cases the second and third urines will show a lower WBC and bacterial count and the prostatic fluid does t show bacteria. There is usually significant growth in n-bacterial prostatitis, but there may be a very high WBC count in the prostatic fluid (Table FVC). There may be difficulties in the diagsis when the WBC is only moderately raised (Table IVD), and the Stamey test may need repeating before a definite diagstic conclusion can be drawn. Examination of the prostatic fluid is important (Meares, 980). The WBC count in prostatitis may be very high (up to 5000 per ml) and alterations in biochemical values besides culture may confirm the presence of bacterial prostatitis. Changes occur in the ph value, specific gravity and prostatic antibacterial factor, assumed to be the zinc concentration (Fair, Couch & Wehner, 976).

5 Prostatitis: diagsis and management Table m. Examples of the Stamey test (urethral) Urines 2 (bladder) (prostatic) Prostatic fluid WBC per /il A Bacterial counts/l Bacterial species WBC per /il B Bacterial counts/l Bacterial species <0 4 Conclusion: <0 4 5xl0 4 E. coli chronic bacterial prostatitis Proteus mirabilis Conclusion: UTI but associated CBP repeat after treatment for UTI (see C) WBC per /il C Bacterial counts/l Bacterial species 2 <0 4 >0* 3 <0 4 Conclusion: UTI cleared with improved prostatitis but still infected WBC per /il D Bacterial counts/l Bacterial species E. coli 0 7 CBP, chronic prostatitis. Conclusion: UTI without associated prostatitis Table IV. Examples of the Stamey test (urethral) Urines 2 (bladder) (prostatic) x0* E. coli 335 2x0* 0 5xlO 3 P. mirabilis 5 Prostatic fluid WBC per /il A Bacterial counts/l 5x0* 2x0* 22x0* Bacterial species Streptococcus mitis S. mitis Conclusion: CBP with mild prostatic urethra spillage WBC per /il 40 2 B Bacterial counts/l 2xlO 5 Bacterial species S. mitis Conclusion: possible CBP. Is the S. mitis really in the prostate? WBC per /il 75 0 C Bacterial counts/l < 0* < 0* Bacterial species Conclusion: NBP WBC per/il 5 2 D Bacterial counts/l < 0* < 0* Bacterial species Conclusion: possible NBP CBP, chronic bacterial prostatitis; NBP, n-bacterial prostatitis xlo x 0* S. mitis

6 6 D. A. Leigh Seminal fluid examination Where the man has testicular or ejaculation pain or discomfort, it is important to examine a specimen of seminal fluid. In some cases the symptoms may be due to an epididymitis or seminal vesiculitis. Examination of a seminal fluid may be misleading for several reasons. The ejaculate is a mixture of prostatic fluid and semen and will usually contain urethral bacteria. Urine should be passed before collection of the seminal fluid, and cleaning and drying of the glans penis should always be carried out. Seminal vesiculitis may occur independently of prostatitis but commonly infection spreads from the prostate (Stewart, 988). The seminal fluid should be examined for fertility as chronic bacterial prostatitis may be associated with a diminution of the sperm count. The WBC may come from the prostatic fluid rather than semen but microbiology is important. In male patients where prostatic massage has been unsuccessful, seminal fluid examination may be very helpful in the diagsis of bacterial prostatitis. Other investigations There are a series of other investigations that can be helpful in confirming prostatitis but t always in confirming the presence of infection. Immuglobulins. The immune response to bacterial prostatitis occurs both as a systemic and local prostate phemen (Shortliffe, Wehner & Stamey, 98). The measurement of IgG, IgA and IgM may be helpful. Antigen-specific immuglobulins may be helpful in determining the response to treatment in patients with enterobacterial infections (Shortliffe & Wehner, 986). The response in serum and prostatic fluid following chemotherapy may show whether treatment has been successful (Meares, 99). Ultrasonic examination. The place of intraveus pyelography and urethrocystoscopy in men with prostatic symptoms is limited, but ultrasonic examination may be helpful in diagsing prostatic abrmalities (Hendrikx et al., 988; Doble & Carter, 989). Bacteriology of bacterial prostatitis Bacteria causing acute prostatitis are commonly Escherichia coli and other Enterobacteriaceae (Stamey, 98), and in hospital cases, pseudomonas, enterococci and Staphylococcus aureus may occur. In chronic bacterial prostatitis findings vary. Many workers report the same bacterial species as in acute bacterial prostatitis (Meares, 987) but there is a group of patients in whom many species of streptococci including enterococci and anaerobes are isolated. Whilst the urethra may be colonized by these bacteria together with Staphylococcus epidermidis, micrococci and diphtheroids, streptococci may occasionally be the infecting organism and the clinical response to treatment can be good. If doubtful pathogens have been isolated in the presence of prostatitis symptoms, the Stamey test must be repeated. S. epidermidis may t be a pathogen in chronic prostatitis, but if present can affect prostatic function as in-vitro studies have shown a reduced function of polymorphonuclear leucocytes, reduction of chemotaxis, phagocytosis and intracellular killing, but the clinical importance of these findings is unclear (Wedven, 989).

7 Prostatitis: diagsis and management 7 Whilst some bacterial species are recognized pathogens in the prostate, there are many difficulties in interpreting the significance of other species. Treatment of bacterial prostatitis The pharmacokinetics of many antimicrobial compounds shows that they diffuse poorly into the prostatic gland. There may be a significant difference in the concentration in interstitial fluid and stroma and prostatic fluid but the fluid level appears clinically important. Prostatic fluid has a ph of 6-4 or less which is more acidic than plasma (ph 7-4) so basic compounds diffuse better than acidic compounds. Lipid solubility is ather important factor in diffusion. In acute bacterial prostatitis there is an intense inflammation and this may allow ready diffusion of all antibiotic compounds. In chronic bacterial prostatitis there may be changes in the prostatic fluid which influences diffusion but single factor other than ph is important. /?-Lactam antibiotics are poor diffusers unless there is heavy inflammation when larger doses are required. Trimethoprim achieves high levels in prostatic fluid, although the clinical success rate of co-trimoxazole is only about 30-40% (Schaeffer, 990). Erythromycin (for appropriate pathogens) and the tetracyclines are successful as long-term suppressive treatments. Quilones diffuse readily into the prostate (Naber, 989; Aagaard & Madsen, 99), although very high levels are t found on routine dosage. Ofloxacin and temafloxacin show the highest levels in prostatic fluids, mainly due to their higher plasma concentrations. The clinical results with the quilones are good (Remy et ai, 988; Childs, 990; Guibert, Boutelier & Guyot, 990; Schaeffer & Darras, 990). Azithromycin achieves high prostatic fluid levels and may be useful for susceptible organisms. The main principles of treatment of bacterial prostatitis are to use high doses for a prolonged course (4-28 days). The Stamey test should be repeated during therapy to confirm eradication. It is necessary to obtain prostatic fluid after massage as the prostatic urine specimen in the Stamey test will contain high levels of the antibiotic which may alter the culture results. It is also necessary to follow up the patient with Stamey tests at intervals to confirm eradication. Other treatment Non-bacterial prostatitis and prostatodynia may be very difficult to treat effectively. Whilst antibiotic therapy is frequently initially given and tetracycline or erythromycin are often successful, the clinical response may be poor. Anti-inflammatory agents, such as ibuprofen may be helpful, particularly when the symptoms are bad. Patients with n-bacterial prostatitis are a complex group and many different therapies may be helpful. Those with a congested prostate may be relieved by regular prostatic massage. Ather small group may respond to zinc sulphate for 28 days as the prostatitis is mainly due to a low zinc concentration in the prostate which is primarily responsible for the antibacterial action of prostatic fluid (Fair et al., 976). The patient should exercise regularly, t with very active sports which may have effect, but travelling by foot for several miles each day. As n-bacterial prostatitis is a complex aetiological group all forms of therapy should be tried as it is impossible to predict the correct therapy. Prostatodynia patients

8 8 D. A. Leigh may have the bladderneck/urethral spasm syndrome and may respond to a-blocking agents. Diazepam may be helpful in relieving the symptoms. Stress, anxiety and depression may play a primary role in prostatodynia and psychiatric help may be indicated in men who do t respond to medical therapy. Summary The investigation of patients with symptoms of prostatitis is complex and prolonged. Non-bacterial prostatitis and prostatodynia are very common (about 90%) and need many varieties of therapy (often t antimicrobial), as particular treatments may be relevant to each patient. Bacterial prostatitis has two distinct clinical syndromes. Acute prostatitis is a severe infection with marked symptoms. Diagsis by urine culture is t difficult and response to antimicrobial therapy is rapid. Chronic bacterial prostatitis requires comprehensive bacteriology investigation using the Stamey test, and culture of prostatic fluid and, in some cases, seminal fluid. The infecting pathogens are variable and including streptococci as well as the usual urinary pathogens such as E. coli and Enterobacteriaceae. Response to antimicrobial therapy is variable and prolonged courses of treatment may be required. Prostatitis syndromes appear to be increasing and affect men of a wide age range. The range of antimicrobial compounds available for treatment has been increased due to the introduction of the quilones and azithromycin but more systematic studies are needed to find features which facilitate the diagsis. References Aagaard, J. & Madsen, P. O. (99). Bacterial prostatitis, new methods of treatment. Urology 37, Suppl. 3, 4-8. Brunner, H., Weidner, W. & Schiefer, H. G. (983). Studies of the role of Ureaplasma weajyticum and Mycoplasma hominis in prostatitis. Journal of Infectious Diseases 47, Childs, S. J. (990). Ciprofloxacin in the treatment of chronic bacterial prostatitis. Urology 35, Suppl. 7, 5-8. Doble, A. & Carter, S. St. C. (989). Ultrasographic findings in prostatitis. Urologic Clinics of North America 6, Drach, G. W., Fair, W. R., Meares, E. M. & Stamey, T. A. (978). Clarification of benign diseases associated with prostatic pain: prostatitis or prostatodynia? Journal of Urology 20, 266. Fair, W. R., Couch, J. A. & Wehner, N. (976). Prostatic antibacterial factor identity and significance. Urology 7, Guibert, J., Boutelier, R. & Guyot, A. (990). A clinical trial of pefloxacin in prostatitis. Journal of Antimicrobial Chemotherapy 26, Suppl. B, 6-6. Hendrikx, A. J. M., Duesburg, W. H., Reintfes, A. G. M., Striok, S. P. & Debruyne, F. M. J. (988). Effectiveness of ultrasound in the pre-operative evaluation of patients with prostatism. Prostate 3, Lipsky, B. A. (989). Urinary tract infections in man. Annals of Internal Medicine 0, Meares, E. M. (980). Prostatitis syndromes: new perspectives about old lores. Journal of Urology 23, 4-7. Meares, E. M. (987). Acute and chronic prostatitis. Diagsis and treatment. Infectious Disease Clinics of North America, Meares, E. M. (99). Prostatitis. Medical Clinics of North America 75, Meares, E. M. & Stemey, T. A. (968). Bacteriologic localization patterns in bacterial prostatitis and urethritis. Investigative Urology 5,

9 Prostatitis: diagsis and management 9 Naber, K. G. (989). Use of quilones in urinary tract infections and prostatitis. Reviews of Infections Diseases, Suppl. 5, Rcmy, G., Rovecr, C, Chavanet, P., Bernard, E., Cellaminica, D. & Portier, H. (988). Use of ofloxacin for prostatitis. Reviews of Infectious Disease 0, Suppl. 5, Schaeffer, A. J. (990). Diagsis and treatment of prostatic infections. Urology 36, Suppl. 5, 3-6. Schaeffer, A. J. & Darras, F. S. (990). The efficacy of rfloxacin in the treatment of chronic bacterial prostatitis refractory to trimethoprim-sulphamethoxazole and/or carbenicillin. Journal of Urology 44, Shortliffe, L. M. D. & Wehner, N. (986). The characterization of bacterial and n-bacterial prostatitis by prostatic immuglobulins. Medicine 65, 399. Shortliffe, L. M. D., Wehner, N. & Stamey, T. A. (98). The detection of a local prostatic immulogic response to bacterial prostatitis. Journal of Urology 25, 509. Stamey, T. A. (98). Prostatitis. Journal of the Royal Society of Medicine 74, Stewart, C. (988). Prostatitis. Emergency Medicine Clinics of North America 6, 39^402. Wedven, H. (989). On chronic prostatitis with special studies of Staphylococcus epidermidis. Scandinavian Journal of Urology and Nephrology Suppl. 23, -36.