C Diagnosis and Management of O N Acute and Chronic T I N Daniel A. Shoskes Floyd Katske U Sun Kim I N G rostatitis syndromes pre- Prostatitis syndromes are some of the most poorly understood yet sent an interesting con- prevalent problems in . There is little controversy over acute trast in incidence and prostatitis, a urinary tract infection with systemic symptoms and E understanding. Acute and signs that typically responds to antimicrobial therapy. By contrast, D Pchronic bacterial prostatitis are the chronic prostatitis syndromes have so far eluded attempts to relatively uncommon, but well- U understand their pathophysiology and design effective therapies, C understood urinary tract infec- resulting in great frustration among patients and health care tions caused by established providers. An accurate diagnosis and a multidisciplinary approach A uropathogens. They are typically T responsive to appropriate antimi- are essential to assist men with this often debilitating condition. crobial therapy. By contrast, the I much more common nonbacteri- O Objectives al prostatitis and prostatodynia N syndromes remain an enigma, This educational activity is designed for nurses and other health both in etiology, appropriate care professionals who care for and educate patients regarding acute workup, and therapy. The rough- and chronic prostatitis. The multiple choice examination that follows ly 2 million annual outpatient is designed to test your achievement of the following educational objec- visits for chronic prostatitis in tives. After studying this offering, you will be able to: the United States (Collins, 1. Define acute and chronic prostatitis. Stafford, O’Leary, & Barry, 1998) 2. Discuss the diagnosis of acute and chronic prostatitis. usually lead to antimicrobial 3. Describe the therapeutic options for treating acute and chronic pro- therapy without an attempt to statitis. document the presence of pro- static infection. This results in very low durable response rates. symptoms for years to decades, suprapubic tenderness and an Despite this, non-antimicrobial leading to depression, job loss, extremely tender . It is alternatives with documented and even suicide. By objective important to avoid vigorous pal- scientific benefit are limited, measures the impact of chronic pation or intentional prostatic often leading to a defeatist pos- prostatitis on quality of life is in patients with pre- ture by both patient and doctor. similar to that of Crohn’s disease sumed , as it may Some patients have persistent (Wenninger, Heiman, Rothman, provoke bacteremia and septic Berghuis, & Berger, 1996). shock. Urinalysis usually reveals elevated WBC and RBC counts Acute Prostatitis and urine culture will be represen- Daniel A. Shoskes, MD, FRCS(c), is Director for Renal Transplant, Acute prostatitis is an acute tative of intra-prostatic organisms. Cleveland Clinic Florida, Fort systemic illness usually caused by Blood analysis should include a Lauderdale, FL. uropathogenic bacteria in the CBC and blood cultures, but not a prostate leading to a febrile uri- PSA, which will be elevated in Floyd Katske, MD, is Assistant nary tract infection. Patients com- most patients due to the acute Clinical Professor, Department of plain of a sudden onset of fever, inflammation. Urology, UCLA School of Medicine, chills, perineal pain, and lower For patients with signs of sep- Torrance, CA. urinary tract symptoms such as sis, therapy for acute prostatitis frequency, urgency, dysuria, noc- begins with appropriate fluid Sun Kim, MD, is a Urology Resident, turia, and even urinary retention. resuscitation and systemic antibi- Department of Urology, UCLA School of Medicine, Torrance, CA. Physical examination may reveal otics, such as ampicillin and an

UROLOGIC NURSING / August 2001 / Volume 21 Number 4 255 C aminoglycoside, targeted at gram- age of presentation in the mid prognosis or response to therapy. O negative pathogens. For patients 40s. Onset may be gradual or Indeed, fewer than 50% of urolo- in urinary retention, a suprapubic sudden, but few patients give a gists or primary care physicians N catheter is preferable to a urethral history of prior acute prostatitis. surveyed even examine ex- T Foley catheter, which may be dif- History of urethral discharge or pressed prostatic secretions let I ficult to place and produce penile lesions may indicate ure- alone perform the entire protocol intense pain. Effective empirical thritis or other sexually transmit- (Moon, 1997). The classification N choices for oral antimicrobial ted disease (STD). Patients often system is based upon the culture U therapy (until culture with sen- have a strong belief that they and examination of first voided I sitivities are available) include have identified the instigating urine (VB1), mid-stream urine TMP-SMX (Septra®, Bactrim®) or cause, usually related to a sexual (VB2), expressed prostatic secre- N a fluoroquinolone (Cipro®, encounter or significant increase tions (EPS), and post-prostatic G Floxin®, Levaquin®). These med- in stress. Symptoms may either massage urine (VB3). Patients ications should be continued for be severe, leading to immediate with positive bacterial cultures E 30 days. In patients not immedi- medical consultation, or so mild that localize to the EPS and/or ately responsive to these thera- that the patient waits months VB3 samples are classified as D pies or with a very fluctuant before seeking care. chronic bacterial prostatitis U prostate, prostatic abscess should A thorough physical exami- (CBP). C be considered and diagnosed by nation focusing on the abdomen Standard teaching requires CT scan or transrectal ultrasound. and pelvis is essential, particular- that the cultured organisms be A While the standard therapy for ly to rule out other pathology that established uropathogens and T prostatic abscess has been may produce urogenital pain (for that patients have recurrent uri- I drainage via transurethral resec- example, inguinal hernia, varico- nary tract infections with these tion, recent reports suggest trans- cele). The is prostatic organisms, although the O perineal or transrectal drainage performed with the patient stand- rationale for these latter require- N under guidance of transrectal ing and leaning over the examin- ments has never been scientifi- ultrasound is equally effective ing table and supporting his cally validated. By this defini- and avoids a surgical procedure. weight on one elbow, a position tion, probably fewer than 5% of Immunocompromised patients which aids in relaxation of the chronic prostatitis patients have and diabetics are particularly at buttock and leg muscles. At the CBP. risk for prostatic abscess caused start of the rectal examination, the In patients without positive by atypical organisms including surrounding pelvic muscles localizing cultures, further classi- gram-positive bacteria and fungi. should first be palpated to search fication is based on the number Once therapy is completed and for painful muscle spasm. The of WBCs per high-power field the acute prostatitis resolved, prostate in chronic prostatitis may (40x objective) in a wet mount of patients should be reassessed for be small or enlarged, boggy or EPS. Patients with an excessive risk factors such as significant firm, and mildly uncomfortable to number of WBCs are classified as prostatic hypertrophy or ineffi- excruciatingly painful. Enlarged having nonbacterial prostatitis cient voiding with high residual may be palpable (NBP) and those without classi- urines. as well, particularly in small and fied as having prostatodynia. thin patients. Prostate massage is While many authors use 10 WBC Chronic Prostatitis accomplished with a rolling per hpf as their upper limit of The chronic prostatitis syn- motion of the examining finger normal for EPS, this number has dromes are characterized by uro- from lateral to medial and then not been firmly established. genital pain, often associated from superior to inferior. Ex- Clearly many patients with chron- with voiding symptoms and erec- pressed fluid is collected into a ic prostatitis fluctuate between tile dysfunction. These symp- sterile container held by the low and high WBC counts over toms may be continuous, inter- patient under the penis. A glass time (Wright, Chmiel, Grayhack, mittent, or relapsing. Pain may slide is touched to the penis to & Schaeffer, 1994), and many be felt in the perineum, penis, collect the last drop for asymptomatic patients have scrotum, lower abdomen, back, microscopy. counts in the abnormal range. or groin. Hematuria is rare, but For the past 30 years, the Realizing that the full “4 hematospermia is more common. classification system devised by glass” test is rarely performed Patients may feel relief after ejac- Meares and Stamey has been the and seldom guides treatment, it ulation, or have severe post-ejac- standard used (see Table 1). is still important to thoroughly ulatory pain as their primary However, this system has never rule out infection in these symptom. Age of onset begins in been validated or shown to dif- patients, at least at the initial late adolescence, with a median ferentiate patients on the basis of consultation. At a minimum

256 UROLOGIC NURSING / August 2001 / Volume 21 Number 4 Table 1. C Classification Systems for Chronic Prostatitis/Chronic Pelvic Pain Syndrome O Acute EPS/VB3 Elevated WBC in Meares-Stamey N UTI? Culture EPS or VB3? Classification NIH Classification Comments T Yes + + Acute prostatitis Category I Urine culture sufficient to I diagnose. N

No + + or - Chronic bacterial Category II Some require recurrent UTI U with uropathogens. I N No - + Nonbacterial Category IIIa WBC elevation may be intermittent. G

No - - Prostatodynia Category IIIb Must rule out other pelvic pathology. E D No + or - + or - None Category IV Asymtomatic U UTI: Urinary tract infection C EPS: Expressed prostatic secretions A VB3: Post prostatic massage urine T I patients should have pre and should undergo urodynamics to Management O post prostatic massage urine rule out bladder/bladder neck The mainstay of therapy for N samples cultured, with a prefer- pathology. Finally, in men with men with category II (chronic ence for EPS microscopy and cul- chronic bacterial prostatitis and bacterial) prostatitis is antibi- ture. A urethral swab for culture those with symptoms suggesting otics, using agents with high pen- of bacteria and STDs and a seminal vesicle or testicular etration into the prostatic fluid as culture are indicated, involvement, a transrectal ultra- well as a spectrum of activity to especially for patients with post sound can demonstrate central include the most common organ- ejaculatory pain that may point prostatic stones or evidence of isms. Features that allow prostat- to an infection of the seminal ejaculatory duct obstruction. ic penetration include lipid solu- vesicles. A serum PSA is essen- A recent NIH consensus con- bility and a high pKa. Commonly tial for men over 45 years of age ference was held on the subject of used agents that fulfill these cri- and in any man with a palpable chronic prostatitis (Nickel, teria include the sulfas (for abnormality of prostatic contour. Nyberg, & Hennenfent, 1999) and example, Septra), the fluro- It is important to realize that a new classification system pro- quinolones (for example, Cipro, inflammation and infection of posed (see Table 1). Acute prosta- Levaquin), the erythromycins (for the prostate can significantly ele- titis is replaced by category I, example, Zithromax®, Biaxin®), vate serum PSA and yield a low chronic bacterial prostatitis and the tetracyclines (for exam- free:total PSA ratio (unlike the replaced by category II, nonbacte- ple, Minocin®). Therapy is com- high ratio found more commonly rial prostatitis replaced by catego- monly continued for at least 6 in BPH). Men with elevated ry IIIa, and prostatodynia re- weeks and the patient then recul- screening PSA values who admit placed by category IIIb. Category tured. Some men, particularly to symptoms of prostatitis are III patients collectively are now those with enlarged boggy pro- often best served by repeating the referred to as having chronic states with large volumes of EPS, test after a course of antibiotics, pelvic pain syndrome (CPPS), a may benefit from regular prostatic which may return the PSA to a change that reflects the predomi- massage combined with the normal level, avoiding an unnec- nance of pain in these patients antibiotics (Nickel, Alexander et essary biopsy. and the uncertainty of the role of al., 1999). Cystoscopy is seldom neces- the prostate in producing the In patients with relapsing sary, and should only be used if symptoms. A new category IV infections, a transrectal ultra- other pathology such as urethral designates asymptomatic patients sound may reveal prostatic calci- stricture or carcinoma in situ is who have evidence for prostatic fication. While diffuse calcifica- strongly suspected. Men with inflammation, either in the EPS or tion along the surgical capsule of significant voiding dysfunction in prostate tissue biopsies. the prostate is a common finding

UROLOGIC NURSING / August 2001 / Volume 21 Number 4 257 C Table 2. patients with a trial of an ery- O Therapeutic Options in Nonbacterial Prostatitis thromycin or tetracycline to rule (NIH Category IIIa) out the possibility. Careful cul- N tures of EPS will often show T First Line growth of gram-positive organ- I ❏ Empiric antibiotic therapy (quinolone, erythromycin, or tetracycline isms such as Staphyloccocus epi- class) dermidis or Corynebacterium. N ❏ Prostatic massage +/- antibiotic therapy Transperineal biopsies will often U ❏ Alpha blocker (for example, tamsulosin) +/- antibiotic therapy grow bacteria not found by other I ❏ Bioflavonoid phytotherapy (for example, quercetin, Prosta-Q®) means (Berger, Krieger, Rothman, N ❏ Finasteride Muller, & Hillier, 1997). It may be ❏ Supportive measures (see Table 4) that these bacteria escape detec- G tion and conventional treatment Second Line (anecdotal data) because they are protected with- E ❏ Intraprostatic injection of antibiotics in biofilms in the prostatic tissue ❏ Allopurinol (Nickel, Costerton, McLean, & D Olson, 1994). ❏ Antifungal therapy and diet modifications Ribosomal RNA techniques U ❏ Cytoreductive prostatic therapy (for example, transurethral (16S), used to detect bacterial sig- C microwave therapy) nal in the prostatic fluid of men A with negative cultures, demon- T strated that the presence of bacte- rial signal by this technique pre- I Table 3. dicted response to empiric Therapeutic Options in Prostatodynia O antibiotic therapy (Tanner, (NIH Category IIIb) N Shoskes, Shahed, & Pace, 1999). ❏ We have identified novel bacteri- Pelvic muscle physiotherapy al sequences which map closest ❏ ® Bioflavonoid phytotherapy (for example, quercetin, Prosta-Q ) to the Corynebacteria which we ❏ Alpha blocker (for example, tamsulosin) have not found in any control or ❏ Neuromuscular pain agents (for example, gabapentin, tricyclic anti- BPH patients. While it is not yet depressants) possible to identify which bacte- ❏ Very important to rule out other causes of pain unrelated to prostate ria present in an EPS sample are (for example, hernia, interstitial cystitis, urinary tract stone) acting as true pathogens and which may be commensals or contaminants, it is our philoso- phy to first treat and eradicate in men with and without prosta- egory IIIa and IIIb; nonbacterial these bacteria and assess the titis and requires no therapy, prostatitis and prostatodynia) impact on symptoms. This larger stones located more cen- who remain the true therapeutic approach is effective in about trally could represent a bacterial challenge (see Tables 2 & 3). one-third of patients (Shoskes & focus and these patients may Suggested etiologies for these Zeitlin, 1999). benefit from transurethral resec- disorders include occult infec- An autoimmune or inflamma- tion of these stones. For men tion, neurogenic bladder, an tory reaction is suggested by the without an anatomic focus who autoimmune or other inflamma- elevation of seminal cytokines in recur despite antibiotics with or tory reaction, neuromuscular these patients and by our own without prostatic massage, pelvic muscle spasm, or sterile observation that markers of oxi- longer courses of suppressive urinary reflux into the prostate. dant stress are significantly ele- antibiotics may be necessary. For Due to the similarities in symp- vated in patients with CPPS men on prolonged antibiotic toms with bacterial prostatitis, an (submitted manuscript). Some pa- therapy, it is important to be vig- occult infection with difficult-to- tients do report benefit with nons- ilant for complications that can culture or entrapped micro- teroidal anti-inflammatories; how- occur with each class of agents organisms has been suspected. ever, long-term use is limited by and monitor for their occurrence The evidence for involve- the toxicity of these agents. (for example, tendon inflamma- ment of Mycoplasma, Urea- Whether the newer cox-2 in- tion with quinolones, photosen- plasma, and Chlamydia is incon- hibitors will be of added benefit is sitivity with tetracyclines). clusive; nevertheless most urolo- currently under study. Brief trials It is patients with CPPS (cat- gists will treat category IIIa of corticosteroids have also been

258 UROLOGIC NURSING / August 2001 / Volume 21 Number 4 tried with mixed results. Table 4. C Anecdotally, we have a patient Supportive Measures for Patients with Chronic Prostatitis O with a renal transplant who suf- (NIH Categories II and III ) fered recurrent CPPS pre-trans- N plant but who has been asympto- ❏ Hot baths T matic since his transplant on full ❏ Nonsteroidal anti-inflammatory agents I cyclosporine-based immunosup- ❏ Avoid alcohol, spicy foods, and caffeine N pression. Clearly, the long-term ❏ Avoid repetitive perineal trauma (for example, mountain bike riding) complications associated with ❏ Inflatable donut to sit on for prolonged periods of sitting U immunosuppression effectively ❏ Stress reduction counseling I contraindicates its use. Phyto- therapy with quercetin, which is a N plant-derived polyphenolic com- G pound with anti-inflammatory Table 5. and anti-oxidant properties, has Internet Resources E been shown to significantly D improve symptoms of men with ❏ Prostatitis Foundation: http://www.prostatitis.org CPPS (Shoskes, 1998). In a ran- ❏ Interstitial Cystitis Collaborative Network: http://www.icn.org U domized, prospective, placebo ❏ Cleveland Clinic Florida Prostatitis Clinic: http://www.dshoskes.com C controlled trial, 82% of men with ❏ CPPS treated with quercetin (in Institute for Male Urology: http://www.urol.com A ❏ the form of the supplement Prostatitis Newsgroup: sci.med.prostate.prostatitis T Prosta-Q®) had a significant I improvement in symptom score, as compared with 20% of men O treated with placebo (Shoskes, which can be diagnosed by clas- men’s lives leading to stress, N Zeitlin, Shahed, & Rajfer, 1999). sical findings on cystoscopy depression, and even suicide. In men whose CPPS is asso- under anesthesia. Other second- Some have suggested a subset of ciated with voiding dysfunction, line therapies with anecdotal evi- these men have a primary psy- urodynamics may show bladder dence of efficacy are listed in chologic disorder with somatiza- outflow obstruction from pseu- Table 2. tion of symptoms to the lower dodyssynergia (Kaplan et al., In patients with no evidence urinary tract. Indeed, men with 1997). Whether this abnormal of infection or inflammation (cat- chronic genital pain have a sig- voiding pattern is secondary to egory IIIb), CPPS may be related nificant incidence of emotional initial infection or inflammation to pelvic floor myalgia. This may loss at onset of symptoms and or whether it is a primary disor- be appreciated on physical exam- many lack social supports der is not known. Nevertheless, ination as previously described, (Schover, 1990). As with all therapy with an alpha blocker, or inferred from lack of response chronic pain disorders, it can be either alone or in combination to antimicrobial or anti-inflam- very difficult to isolate cause and with antibiotics (Barbalias, matory therapy. Therapeutic effect when dealing with psycho- Nikiforidis, & Liatsikos, 1998) or options are outlined in Table 3. logic problems. Nevertheless, it bladder retraining with biofeed- Supportive measures, which may is important to understand the back (Kaplan et al., 1997) are improve symptoms in all impact on quality of life that effective. In the younger men patients with chronic prostati- these men may suffer and to offer typical of CPPS patients, tamsu- tis/CPPS, include pelvic physio- appropriate referral to counsel- losin is the most easily tolerated therapy, local heat, and avoiding ing, even as an adjunct to other of the alpha blockers because it alcohol, spicy foods, and caffeine therapies (see Table 5). lacks anti-hypertensive effects. (see Table 4). Systemic neuro- Preliminary studies suggest that muscular relaxants may also be Summary finasteride may also benefit men of help, although side effects Prostatitis syndromes remain with CPPS, but whether this is often limit their use. Anecdotal a diagnostic and therapeutic chal- due to shrinkage of the prostate or evidence suggests that gaba- lenge. Infection should always be another unrelated mechanism is pentin (Neurontin®), often com- searched for first and eradicated. not known (Leskinen, Lukkarinen, bined with a low-dose tricyclic If symptoms persist, therapies tar- & Marttila, 1999). Men with antidepressant, may be of value geted to inflammation, such as prominent dysuria or voiding dys- in these patients. NSAIDs or quercetin, should be function associated with their Chronic prostatitis can have tried. Pelvic-muscle spasm and pain may have interstitial cystitis, a major psychological impact on voiding dysfunction will often

UROLOGIC NURSING / August 2001 / Volume 21 Number 4 261 C improve with alpha blockers, Muller, C.H., & Hillier, S.L. (1997). blind, placebo-controlled, pilot Bacteria in the prostate tissue of men study. Urology, 53(3), 502-505. O physiotherapy, systemic muscle relaxants, and other supportive with idiopathic prostatic inflamma- Moon, T.D. (1997). Questionnaire survey N tion. Journal of Urology, 157(3), 863- of urologists and primary care physi- therapy. Perseverance and cre- 865. cians’ diagnostic and treatment prac- T ativity in therapy can lead to Collins, M.M., Stafford, R.S., O’Leary, tices for prostatitis. Urology, 50(4), I durable improvement in the M.P., & Barry, M.J. (1998). How com- 543-547. majority of men with this debili- mon is prostatitis? A national survey Nickel, J.C., Alexander, R., Anderson, R., N of physician visits. Journal of Krieger, J., Moon, T., Neal, D., tating condition. New therapies Urology, 159(4), 1224-1228. Schaeffer, A., & Shoskes, D. (1999). U must be evaluated scientifically Kaplan, S.A., Santarosa, R.P., D’Alisera, Prostatitis unplugged? Prostatic I using validated instruments for P.M., Fay, B.J., Ikeguchi, E.F., massage revisited. Tech Urology, symptom severity and quality of Hendricks, J., Klein, L., & Te, A.E. 5(1), 1-7. N (1997). Pseudodyssynergia (contrac- Nickel, J.C., Costerton, J.W., McLean, R.J.C., life improvement. ¥ tion of the external sphincter during & Olson, M. (1994). Bacterial biofilms: G voiding) misdiagnosed as chronic Influence on the pathogenesis, diag- References nonbacterial prostatitis and the role nosis, and treatment of urinary tract Barbalias, G.A., Nikiforidis, G., & of biofeedback as a therapeutic infections. Journal of Antimicrobial E Liatsikos, E.N. (1998). Alpha-block- option. Journal of Urology, 157(6), Chemotherapy, 33(Suppl. A), 31-41. D ers for the treatment of chronic pro- 2234- 2237. Nickel, J.C., Nyberg, L.M., & Hennenfent, statitis in combination with antibi- Leskinen, M., Lukkarinen, O., & Marttila, M. (1999). Research guidelines for U otics. Journal of Urology, 159(3), T. (1999). Effects of finasteride in chronic prostatitis: Consensus report 883-887. patients with inflammatory chronic from the first National Institutes of C Berger, R.E., Krieger, N., Rothman, I., pelvic pain syndrome: A double- Health International Prostatitis A Collaborative Network. Urology, 54(2), 229-233. T Schover, L.R. (1990). Psychological factors I in men with genital pain. Cleveland Clinic Journal of Medicine, 57(8), O 697-700. ARE YOU READY FOR A CHANGE Shoskes, D.A. (1998). Effect of the N bioflavonoids quercetin and cur- FROM A PURELY CLINICAL cumin on ischemic renal injury: A NURSING PRACTICE? new class of renoprotective agents. Transplantation, 66(2), 147-152. Shoskes, D.A., & Zeitlin, S.I. (1999). Use Clinical Specialist, RN for Houston, TX. of prostatic massage in combination with antibiotics in the treatment of Manufacturer of urology/urodynamic equip- chronic prostatitis. ment. and Prostate Diseases, 2(3), 159-162. Shoskes, D.A., Zeitlin, S.I., Shahed, A., & Raifer, J. (1999). Quercetin in men Responsibilities: Provide clinical phone sup- with category III chronic prostatitis: port to med field, develop clinical procedures & A preliminary prospective, double- training materials, manage edu programs & blind, placebo-controlled trial. Urology, 54(6), 960-963. participate in product development. Tanner, M.A., Shoskes, D., Shahed, A., & Pace, N.R. (1999). Prevalence of Successful candidate will have: Corynebacterial 16S rRNA sequences in patients with bacterial and “non- ¥ Current RN licensure (BSN pref) bacterial” prostatitis. Journal of ¥ 5+ years clinical practice (Mgt. pref) Clinical Microbiology, 37(6), 1863- ¥ Problem solving & communication skills 1870. Wenninger, K.J., Heiman, R., Rothman, ¥ PC, Word, Excel & Power Point A., Berghuis, J.P., & Berger, R.E. (1996). Sickness impact of chronic Urology &/or Urodynamics experience a plus! nonbacterial prostatitis and its corre- lates. Journal of Urology, 155(3), 965-968. Excellent salary & benefits. Will relocate & Wright, E.T., Chmiel, J.S., Grayhack, J.T., train ideal candidate. Mail to Clinical Specialist & Schaeffer, A.J. (1994). Prostatic fluid inflammation in prostatitis. 4235 Greenbriar Dr., Stafford, TX 77477, Journal of Urology, 152(6, Pt. II), fax 281-491-6852, email [email protected]. 2300-2303.

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