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Diagnosis and Management of Acute and Chronic Prostatitis Daniel A. Shoskes Floyd Katske Sun Kim P rostatitis syndromes present an interesting contrast in incidence and understanding. Acute and chronic bacterial prostatitis are relatively uncommon, but wellunderstood urinary tract infections caused by established uropathogens. They are typically responsive to appropriate antimicrobial therapy. By contrast, the much more common nonbacterial prostatitis and prostatodynia syndromes remain an enigma, both in etiology, appropriate workup, and therapy. The roughly 2 million annual outpatient visits for chronic prostatitis in the United States (Collins, Stafford, O’Leary, & Barry, 1998) usually lead to antimicrobial therapy without an attempt to document the presence of prostatic infection. This results in very low durable response rates. Despite this, non-antimicrobial alternatives with documented scientific benefit are limited, often leading to a defeatist posture by both patient and doctor. Some patients have persistent Daniel A. Shoskes, MD, FRCS(c), is Director for Renal Transplant, Cleveland Clinic Florida, Fort Lauderdale, FL. Floyd Katske, MD, is Assistant Clinical Professor, Department of Urology, UCLA School of Medicine, Torrance, CA. Sun Kim, MD, is a Urology Resident, Department of Urology, UCLA School of Medicine, Torrance, CA. Prostatitis syndromes are some of the most poorly understood yet prevalent problems in urology. There is little controversy over acute prostatitis, a urinary tract infection with systemic symptoms and signs that typically responds to antimicrobial therapy. By contrast, the chronic prostatitis syndromes have so far eluded attempts to understand their pathophysiology and design effective therapies, resulting in great frustration among patients and health care providers. An accurate diagnosis and a multidisciplinary approach are essential to assist men with this often debilitating condition. Objectives This educational activity is designed for nurses and other health care professionals who care for and educate patients regarding acute and chronic prostatitis. The multiple choice examination that follows is designed to test your achievement of the following educational objectives. After studying this offering, you will be able to: 1. Define acute and chronic prostatitis. 2. Discuss the diagnosis of acute and chronic prostatitis. 3. Describe the therapeutic options for treating acute and chronic prostatitis. symptoms for years to decades, leading to depression, job loss, and even suicide. By objective measures the impact of chronic prostatitis on quality of life is similar to that of Crohn’s disease (Wenninger, Heiman, Rothman, Berghuis, & Berger, 1996). Acute Prostatitis Acute prostatitis is an acute systemic illness usually caused by uropathogenic bacteria in the prostate leading to a febrile urinary tract infection. Patients complain of a sudden onset of fever, chills, perineal pain, and lower urinary tract symptoms such as frequency, urgency, dysuria, nocturia, and even urinary retention. Physical examination may reveal UROLOGIC NURSING / August 2001 / Volume 21 Number 4 suprapubic tenderness and an extremely tender prostate. It is important to avoid vigorous palpation or intentional prostatic massage in patients with presumed acute prostatitis, as it may provoke bacteremia and septic shock. Urinalysis usually reveals elevated WBC and RBC counts and urine culture will be representative of intra-prostatic organisms. Blood analysis should include a CBC and blood cultures, but not a PSA, which will be elevated in most patients due to the acute inflammation. For patients with signs of sepsis, therapy for acute prostatitis begins with appropriate fluid resuscitation and systemic antibiotics, such as ampicillin and an 255 C O N T I N U I N G E D U C A T I O N C O N T I N U I N G E D U C A T I O N aminoglycoside, targeted at gramnegative pathogens. For patients in urinary retention, a suprapubic catheter is preferable to a urethral Foley catheter, which may be difficult to place and produce intense pain. Effective empirical choices for oral antimicrobial therapy (until culture with sensitivities are available) include TMP-SMX (Septra®, Bactrim®) or a fluoroquinolone (Cipro®, ® ® Floxin , Levaquin ). These medications should be continued for 30 days. In patients not immediately responsive to these therapies or with a very fluctuant prostate, prostatic abscess should be considered and diagnosed by CT scan or transrectal ultrasound. While the standard therapy for prostatic abscess has been drainage via transurethral resection, recent reports suggest transperineal or transrectal drainage under guidance of transrectal ultrasound is equally effective and avoids a surgical procedure. Immunocompromised patients and diabetics are particularly at risk for prostatic abscess caused by atypical organisms including gram-positive bacteria and fungi. Once therapy is completed and the acute prostatitis resolved, patients should be reassessed for risk factors such as significant prostatic hypertrophy or inefficient voiding with high residual urines. Chronic Prostatitis The chronic prostatitis syndromes are characterized by urogenital pain, often associated with voiding symptoms and erectile dysfunction. These symptoms may be continuous, intermittent, or relapsing. Pain may be felt in the perineum, penis, scrotum, lower abdomen, back, or groin. Hematuria is rare, but hematospermia is more common. Patients may feel relief after ejaculation, or have severe post-ejaculatory pain as their primary symptom. Age of onset begins in late adolescence, with a median 256 age of presentation in the mid 40s. Onset may be gradual or sudden, but few patients give a history of prior acute prostatitis. History of urethral discharge or penile lesions may indicate urethritis or other sexually transmitted disease (STD). Patients often have a strong belief that they have identified the instigating cause, usually related to a sexual encounter or significant increase in stress. Symptoms may either be severe, leading to immediate medical consultation, or so mild that the patient waits months before seeking care. A thorough physical examination focusing on the abdomen and pelvis is essential, particularly to rule out other pathology that may produce urogenital pain (for example, inguinal hernia, varicocele). The rectal examination is performed with the patient standing and leaning over the examining table and supporting his weight on one elbow, a position which aids in relaxation of the buttock and leg muscles. At the start of the rectal examination, the surrounding pelvic muscles should first be palpated to search for painful muscle spasm. The prostate in chronic prostatitis may be small or enlarged, boggy or firm, and mildly uncomfortable to excruciatingly painful. Enlarged seminal vesicles may be palpable as well, particularly in small and thin patients. Prostate massage is accomplished with a rolling motion of the examining finger from lateral to medial and then from superior to inferior. Expressed fluid is collected into a sterile container held by the patient under the penis. A glass slide is touched to the penis to collect the last drop for microscopy. For the past 30 years, the classification system devised by Meares and Stamey has been the standard used (see Table 1). However, this system has never been validated or shown to differentiate patients on the basis of prognosis or response to therapy. Indeed, fewer than 50% of urologists or primary care physicians surveyed even examine expressed prostatic secretions let alone perform the entire protocol (Moon, 1997). The classification system is based upon the culture and examination of first voided urine (VB1), mid-stream urine (VB2), expressed prostatic secretions (EPS), and post-prostatic massage urine (VB3). Patients with positive bacterial cultures that localize to the EPS and/or VB3 samples are classified as chronic bacterial prostatitis (CBP). Standard teaching requires that the cultured organisms be established uropathogens and that patients have recurrent urinary tract infections with these prostatic organisms, although the rationale for these latter requirements has never been scientifically validated. By this definition, probably fewer than 5% of chronic prostatitis patients have CBP. In patients without positive localizing cultures, further classification is based on the number of WBCs per high-power field (40x objective) in a wet mount of EPS. Patients with an excessive number of WBCs are classified as having nonbacterial prostatitis (NBP) and those without classified as having prostatodynia. While many authors use 10 WBC per hpf as their upper limit of normal for EPS, this number has not been firmly established. Clearly many patients with chronic prostatitis fluctuate between low and high WBC counts over time (Wright, Chmiel, Grayhack, & Schaeffer, 1994), and many asymptomatic patients have counts in the abnormal range. Realizing that the full “4 glass” test is rarely performed and seldom guides treatment, it is still important to thoroughly rule out infection in these patients, at least at the initial consultation. At a minimum UROLOGIC NURSING / August 2001 / Volume 21 Number 4 Table 1. Classification Systems for Chronic Prostatitis/Chronic Pelvic Pain Syndrome Meares-Stamey Classification NIH Classification + Acute prostatitis Category I Urine culture sufficient to diagnose. + + or - Chronic bacterial Category II Some require recurrent UTI with uropathogens. No - + Nonbacterial Category IIIa WBC elevation may be intermittent. No - - Prostatodynia Category IIIb Must rule out other pelvic pathology. No + or - + or - None Category IV Asymtomatic EPS/VB3 Culture Elevated WBC in EPS or VB3? Yes + No Acute UTI? Comments UTI: Urinary tract infection EPS: Expressed prostatic secretions VB3: Post prostatic massage urine patients should have pre and post prostatic massage urine samples cultured, with a preference for EPS microscopy and culture. A urethral swab for culture of bacteria and STDs and a semen culture are indicated, especially for patients with post ejaculatory pain that may point to an infection of the seminal vesicles. A serum PSA is essential for men over 45 years of age and in any man with a palpable abnormality of prostatic contour. It is important to realize that inflammation and infection of the prostate can significantly elevate serum PSA and yield a low free:total PSA ratio (unlike the high ratio found more commonly in BPH). Men with elevated screening PSA values who admit to symptoms of prostatitis are often best served by repeating the test after a course of antibiotics, which may return the PSA to a normal level, avoiding an unnecessary biopsy. Cystoscopy is seldom necessary, and should only be used if other pathology such as urethral stricture or carcinoma in situ is strongly suspected. Men with significant voiding dysfunction should undergo urodynamics to rule out bladder/bladder neck pathology. Finally, in men with chronic bacterial prostatitis and those with symptoms suggesting seminal vesicle or testicular involvement, a transrectal ultrasound can demonstrate central prostatic stones or evidence of ejaculatory duct obstruction. A recent NIH consensus conference was held on the subject of chronic prostatitis (Nickel, Nyberg, & Hennenfent, 1999) and a new classification system proposed (see Table 1). Acute prostatitis is replaced by category I, chronic bacterial prostatitis replaced by category II, nonbacterial prostatitis replaced by category IIIa, and prostatodynia replaced by category IIIb. Category III patients collectively are now referred to as having chronic pelvic pain syndrome (CPPS), a change that reflects the predominance of pain in these patients and the uncertainty of the role of the prostate in producing the symptoms. A new category IV designates asymptomatic patients who have evidence for prostatic inflammation, either in the EPS or in prostate tissue biopsies. UROLOGIC NURSING / August 2001 / Volume 21 Number 4 Management The mainstay of therapy for men with category II (chronic bacterial) prostatitis is antibiotics, using agents with high penetration into the prostatic fluid as well as a spectrum of activity to include the most common organisms. Features that allow prostatic penetration include lipid solubility and a high pKa. Commonly used agents that fulfill these criteria include the sulfas (for example, Septra), the fluroquinolones (for example, Cipro, Levaquin), the erythromycins (for example, Zithromax®, Biaxin®), and the tetracyclines (for example, Minocin®). Therapy is commonly continued for at least 6 weeks and the patient then recultured. Some men, particularly those with enlarged boggy prostates with large volumes of EPS, may benefit from regular prostatic massage combined with the antibiotics (Nickel, Alexander et al., 1999). In patients with relapsing infections, a transrectal ultrasound may reveal prostatic calcification. While diffuse calcification along the surgical capsule of the prostate is a common finding 257 C O N T I N U I N G E D U C A T I O N C O N T I N U I N G E D U C A T I O N Table 2. Therapeutic Options in Nonbacterial Prostatitis (NIH Category IIIa) First Line ❏ Empiric antibiotic therapy (quinolone, erythromycin, or tetracycline class) ❏ Prostatic massage +/- antibiotic therapy ❏ Alpha blocker (for example, tamsulosin) +/- antibiotic therapy ❏ Bioflavonoid phytotherapy (for example, quercetin, Prosta-Q®) ❏ Finasteride ❏ Supportive measures (see Table 4) Second Line (anecdotal data) ❏ Intraprostatic injection of antibiotics ❏ Allopurinol ❏ Antifungal therapy and diet modifications ❏ Cytoreductive prostatic therapy (for example, transurethral microwave therapy) Table 3. Therapeutic Options in Prostatodynia (NIH Category IIIb) ❏ ❏ ❏ ❏ ❏ Pelvic muscle physiotherapy Bioflavonoid phytotherapy (for example, quercetin, Prosta-Q®) Alpha blocker (for example, tamsulosin) Neuromuscular pain agents (for example, gabapentin, tricyclic antidepressants) Very important to rule out other causes of pain unrelated to prostate (for example, hernia, interstitial cystitis, urinary tract stone) in men with and without prostatitis and requires no therapy, larger stones located more centrally could represent a bacterial focus and these patients may benefit from transurethral resection of these stones. For men without an anatomic focus who recur despite antibiotics with or without prostatic massage, longer courses of suppressive antibiotics may be necessary. For men on prolonged antibiotic therapy, it is important to be vigilant for complications that can occur with each class of agents and monitor for their occurrence (for example, tendon inflammation with quinolones, photosensitivity with tetracyclines). It is patients with CPPS (cat- 258 egory IIIa and IIIb; nonbacterial prostatitis and prostatodynia) who remain the true therapeutic challenge (see Tables 2 & 3). Suggested etiologies for these disorders include occult infection, neurogenic bladder, an autoimmune or other inflammatory reaction, neuromuscular pelvic muscle spasm, or sterile urinary reflux into the prostate. Due to the similarities in symptoms with bacterial prostatitis, an occult infection with difficult-toculture or entrapped microorganisms has been suspected. The evidence for involvement of Mycoplasma, Ureaplasma, and Chlamydia is inconclusive; nevertheless most urologists will treat category IIIa patients with a trial of an erythromycin or tetracycline to rule out the possibility. Careful cultures of EPS will often show growth of gram-positive organisms such as Staphyloccocus epidermidis or Corynebacterium. Transperineal biopsies will often grow bacteria not found by other means (Berger, Krieger, Rothman, Muller, & Hillier, 1997). It may be that these bacteria escape detection and conventional treatment because they are protected within biofilms in the prostatic tissue (Nickel, Costerton, McLean, & Olson, 1994). Ribosomal RNA techniques (16S), used to detect bacterial signal in the prostatic fluid of men with negative cultures, demonstrated that the presence of bacterial signal by this technique predicted response to empiric antibiotic therapy (Tanner, Shoskes, Shahed, & Pace, 1999). We have identified novel bacterial sequences which map closest to the Corynebacteria which we have not found in any control or BPH patients. While it is not yet possible to identify which bacteria present in an EPS sample are acting as true pathogens and which may be commensals or contaminants, it is our philosophy to first treat and eradicate these bacteria and assess the impact on symptoms. This approach is effective in about one-third of patients (Shoskes & Zeitlin, 1999). An autoimmune or inflammatory reaction is suggested by the elevation of seminal cytokines in these patients and by our own observation that markers of oxidant stress are significantly elevated in patients with CPPS (submitted manuscript). Some patients do report benefit with nonsteroidal anti-inflammatories; however, long-term use is limited by the toxicity of these agents. Whether the newer cox-2 inhibitors will be of added benefit is currently under study. Brief trials of corticosteroids have also been UROLOGIC NURSING / August 2001 / Volume 21 Number 4 tried with mixed results. Anecdotally, we have a patient with a renal transplant who suffered recurrent CPPS pre-transplant but who has been asymptomatic since his transplant on full cyclosporine-based immunosuppression. Clearly, the long-term complications associated with immunosuppression effectively contraindicates its use. Phytotherapy with quercetin, which is a plant-derived polyphenolic compound with anti-inflammatory and anti-oxidant properties, has been shown to significantly improve symptoms of men with CPPS (Shoskes, 1998). In a randomized, prospective, placebo controlled trial, 82% of men with CPPS treated with quercetin (in the form of the supplement Prosta-Q®) had a significant improvement in symptom score, as compared with 20% of men treated with placebo (Shoskes, Zeitlin, Shahed, & Rajfer, 1999). In men whose CPPS is associated with voiding dysfunction, urodynamics may show bladder outflow obstruction from pseudodyssynergia (Kaplan et al., 1997). Whether this abnormal voiding pattern is secondary to initial infection or inflammation or whether it is a primary disorder is not known. Nevertheless, therapy with an alpha blocker, either alone or in combination with antibiotics (Barbalias, Nikiforidis, & Liatsikos, 1998) or bladder retraining with biofeedback (Kaplan et al., 1997) are effective. In the younger men typical of CPPS patients, tamsulosin is the most easily tolerated of the alpha blockers because it lacks anti-hypertensive effects. Preliminary studies suggest that finasteride may also benefit men with CPPS, but whether this is due to shrinkage of the prostate or another unrelated mechanism is not known (Leskinen, Lukkarinen, & Marttila, 1999). Men with prominent dysuria or voiding dysfunction associated with their pain may have interstitial cystitis, Table 4. Supportive Measures for Patients with Chronic Prostatitis (NIH Categories II and III ) ❏ ❏ ❏ ❏ ❏ ❏ Hot baths Nonsteroidal anti-inflammatory agents Avoid alcohol, spicy foods, and caffeine Avoid repetitive perineal trauma (for example, mountain bike riding) Inflatable donut to sit on for prolonged periods of sitting Stress reduction counseling Table 5. Internet Resources ❏ ❏ ❏ ❏ ❏ Prostatitis Foundation: http://www.prostatitis.org Interstitial Cystitis Collaborative Network: http://www.icn.org Cleveland Clinic Florida Prostatitis Clinic: http://www.dshoskes.com Institute for Male Urology: http://www.urol.com Prostatitis Newsgroup: sci.med.prostate.prostatitis which can be diagnosed by classical findings on cystoscopy under anesthesia. Other secondline therapies with anecdotal evidence of efficacy are listed in Table 2. In patients with no evidence of infection or inflammation (category IIIb), CPPS may be related to pelvic floor myalgia. This may be appreciated on physical examination as previously described, or inferred from lack of response to antimicrobial or anti-inflammatory therapy. Therapeutic options are outlined in Table 3. Supportive measures, which may improve symptoms in all patients with chronic prostatitis/CPPS, include pelvic physiotherapy, local heat, and avoiding alcohol, spicy foods, and caffeine (see Table 4). Systemic neuromuscular relaxants may also be of help, although side effects often limit their use. Anecdotal evidence suggests that gabapentin (Neurontin®), often combined with a low-dose tricyclic antidepressant, may be of value in these patients. Chronic prostatitis can have a major psychological impact on UROLOGIC NURSING / August 2001 / Volume 21 Number 4 men’s lives leading to stress, depression, and even suicide. Some have suggested a subset of these men have a primary psychologic disorder with somatization of symptoms to the lower urinary tract. Indeed, men with chronic genital pain have a significant incidence of emotional loss at onset of symptoms and many lack social supports (Schover, 1990). As with all chronic pain disorders, it can be very difficult to isolate cause and effect when dealing with psychologic problems. Nevertheless, it is important to understand the impact on quality of life that these men may suffer and to offer appropriate referral to counseling, even as an adjunct to other therapies (see Table 5). Summary Prostatitis syndromes remain a diagnostic and therapeutic challenge. Infection should always be searched for first and eradicated. If symptoms persist, therapies targeted to inflammation, such as NSAIDs or quercetin, should be tried. Pelvic-muscle spasm and voiding dysfunction will often 261 C O N T I N U I N G E D U C A T I O N C O N T I N U I N G improve with alpha blockers, physiotherapy, systemic muscle relaxants, and other supportive therapy. Perseverance and creativity in therapy can lead to durable improvement in the majority of men with this debilitating condition. New therapies must be evaluated scientifically using validated instruments for symptom severity and quality of life improvement. • References E D U C A T I O N Barbalias, G.A., Nikiforidis, G., & Liatsikos, E.N. (1998). Alpha-blockers for the treatment of chronic prostatitis in combination with antibiotics. Journal of Urology, 159(3), 883-887. Berger, R.E., Krieger, N., Rothman, I., Muller, C.H., & Hillier, S.L. (1997). Bacteria in the prostate tissue of men with idiopathic prostatic inflammation. Journal of Urology, 157(3), 863865. Collins, M.M., Stafford, R.S., O’Leary, M.P., & Barry, M.J. (1998). How common is prostatitis? A national survey of physician visits. Journal of Urology, 159(4), 1224-1228. Kaplan, S.A., Santarosa, R.P., D’Alisera, P.M., Fay, B.J., Ikeguchi, E.F., Hendricks, J., Klein, L., & Te, A.E. (1997). Pseudodyssynergia (contraction of the external sphincter during voiding) misdiagnosed as chronic nonbacterial prostatitis and the role of biofeedback as a therapeutic option. Journal of Urology, 157(6), 2234- 2237. Leskinen, M., Lukkarinen, O., & Marttila, T. (1999). Effects of finasteride in patients with inflammatory chronic pelvic pain syndrome: A double- ARE YOU READY FOR A CHANGE FROM A PURELY CLINICAL NURSING PRACTICE? Clinical Specialist, RN for Houston, TX. Manufacturer of urology/urodynamic equipment. Responsibilities: Provide clinical phone support to med field, develop clinical procedures & training materials, manage edu programs & participate in product development. Successful candidate will have: • Current RN licensure (BSN pref) • 5+ years clinical practice (Mgt. pref) • Problem solving & communication skills • PC, Word, Excel & Power Point Urology &/or Urodynamics experience a plus! Excellent salary & benefits. Will relocate & train ideal candidate. Mail to Clinical Specialist 4235 Greenbriar Dr., Stafford, TX 77477, fax 281-491-6852, email [email protected]. 262 blind, placebo-controlled, pilot study. Urology, 53(3), 502-505. Moon, T.D. (1997). Questionnaire survey of urologists and primary care physicians’ diagnostic and treatment practices for prostatitis. Urology, 50(4), 543-547. Nickel, J.C., Alexander, R., Anderson, R., Krieger, J., Moon, T., Neal, D., Schaeffer, A., & Shoskes, D. (1999). Prostatitis unplugged? Prostatic massage revisited. Tech Urology, 5(1), 1-7. Nickel, J.C., Costerton, J.W., McLean, R.J.C., & Olson, M. (1994). Bacterial biofilms: Influence on the pathogenesis, diagnosis, and treatment of urinary tract infections. Journal of Antimicrobial Chemotherapy, 33(Suppl. A), 31-41. Nickel, J.C., Nyberg, L.M., & Hennenfent, M. (1999). Research guidelines for chronic prostatitis: Consensus report from the first National Institutes of Health International Prostatitis Collaborative Network. Urology, 54(2), 229-233. Schover, L.R. (1990). Psychological factors in men with genital pain. Cleveland Clinic Journal of Medicine, 57(8), 697-700. Shoskes, D.A. (1998). Effect of the bioflavonoids quercetin and curcumin on ischemic renal injury: A new class of renoprotective agents. Transplantation, 66(2), 147-152. Shoskes, D.A., & Zeitlin, S.I. (1999). Use of prostatic massage in combination with antibiotics in the treatment of chronic prostatitis. Prostate Cancer and Prostate Diseases, 2(3), 159-162. Shoskes, D.A., Zeitlin, S.I., Shahed, A., & Raifer, J. (1999). Quercetin in men with category III chronic prostatitis: A preliminary prospective, doubleblind, placebo-controlled trial. Urology, 54(6), 960-963. Tanner, M.A., Shoskes, D., Shahed, A., & Pace, N.R. (1999). Prevalence of Corynebacterial 16S rRNA sequences in patients with bacterial and “nonbacterial” prostatitis. Journal of Clinical Microbiology, 37(6), 18631870. Wenninger, K.J., Heiman, R., Rothman, A., Berghuis, J.P., & Berger, R.E. (1996). Sickness impact of chronic nonbacterial prostatitis and its correlates. Journal of Urology, 155(3), 965-968. Wright, E.T., Chmiel, J.S., Grayhack, J.T., & Schaeffer, A.J. (1994). Prostatic fluid inflammation in prostatitis. Journal of Urology, 152(6, Pt. II), 2300-2303. UROLOGIC NURSING / August 2001 / Volume 21 Number 4