From: The Merck Manual of Diagnosis and Therapy

Prostatitis

Acute bacterial prostatitis is characterized by chills, high fever, urinary frequency and urgency, perineal and low back pain, varying degrees of symptoms of obstructed voiding, dysuria or burning on urination, nocturia, sometimes gross hematuria, and often arthralgia and myalgia. The prostate gland is tender, focally or diffusely swollen and indurated, and usually warm when gently palpated in the rectum. Confirmatory laboratory tests include pyuria on urinalysis, positive urine culture, and occasionally positive blood cultures. Culture of prostatic secretions usually yields large numbers of the bacterial pathogen (most commonly enteric, gram-negative). However, because bacteremia may occur, an acutely inflamed prostate gland should not undergo massage until adequate blood levels of an appropriate antibiotic have been established. Because acute cystitis usually soon accompanies acute prostatitis, the bacterial pathogen often can be identified by culture of voided bladder urine.

Treatment includes general support with bed rest, analgesics, stool softeners, and hydration. Initial therapy with a fluoroquinolone twice daily is usually effective and can be given until culture and sensitivity test results are known. If the clinical response is satisfactory, treatment is continued for about 30 days to prevent chronic bacterial prostatitis. If sepsis is suspected, broad-spectrum antibiotics covering gram-positive and gram-negative organisms (eg, a combination of ampicillin and gentamicin) should be given IV until the bacterial sensitivity is known. If the clinical response is adequate, the patient continues IV therapy until afebrile for 24 to 48 h and then is switched to oral therapy. If complete urinary retention occurs, bladder drainage by suprapubic cystostomy is preferred over a urethral catheter (which may lead to bacteremia). Rarely, prostate abscess develops and should usually be treated surgically.

Chronic bacterial prostatitis has variable symptoms, but the hallmark is relapsing UTI due to the same pathogen found in prostatic secretions. Some patients are asymptomatic except for bacilluria that relapses between courses of antibiotics. Most patients, however, experience low back and perineal pain, urinary urgency and frequency, and painful urination. Involvement of the scrotal contents produces intense localizing discomfort, swelling, erythema, and severe tenderness on palpation (see Epididymitis in Ch. 219). On rectal palpation, the prostate may be moderately tender and irregularly indurated or boggy, but there are no specific findings. Secretions may be copious. Numerous WBCs, often in large clumps, and lipid-laden macrophages (oval fat bodies) may be identified, but the number of WBCs does not distinguish bacterial from nonbacterial prostatitis.

Gram-negative bacilli are the most common cause, but enterococci and chlamydiae have also been associated with chronic infection. Oral fluoroquinolone therapy is more effective than trimethoprim-sulfamethoxazole and is usually given twice daily for 4 to 12 wk. Chronic bacterial prostatitis often recurs and is usually treated with a second course of antibiotics. A fluoroquinolone is the treatment of choice.

Chronic nonbacterial prostatitis is more common than bacterial prostatitis. The cause is unknown. Symptoms simulate those of chronic bacterial prostatitis; WBCs and oval fat bodies are usually increased in prostatic secretions. However, a history of UTI is rare. Lower-tract localization cultures of urethral, bladder, and prostatic secretions are required for diagnosis to rule out a bacterial pathogen.

Hot sitz baths, anticholinergic drugs, and periodic prostatic massage (especially for congestive prostatitis) provide some symptomatic relief. Antibiotics do not relieve symptoms, but NSAIDs may be helpful.

Prostatodynia is a noninfectious, noninflammatory condition of younger men. The symptoms mimic those of prostatitis. Usually, no signs of infection or inflammation are present on examination of the urine or prostatic secretions. Treatment is empiric and supportive.

Seminal vesiculitis (inflammation of the seminal vesicles) may cause painless, bloody ejaculate. This uncommon infection is impossible to diagnose by culture techniques. Rarely, transrectal ultrasonography allows aspiration, which confirms the seminal vesicles as the source of blood in the ejaculate. Treatment is supportive.

Prostatitis, Studies and Papers

Here is a study that show how prevalent prostatitis is in men!

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Prostatitis Screening Reduces Unnecessary Biopsies in Men With Elevated PSA

WESTPORT, CT (Reuters Health) Oct 31 - Nearly half of all asymptomatic men with an elevated prostate specific antigen (PSA) level have laboratory signs of prostatitis.

Screening for prostatitis in this population is "safe and effective, and may decrease the number of potentially unnecessary biopsies," Dr. Jeannette M. Potts, of the Cleveland Clinic Foundation, in Ohio, suggests in the November issue of the Journal of Urology.

This is the first prevalence study of the National Institutes of Health category IV prostatitis in asymptomatic in men with an elevated PSA level, according to Dr. Potts. Her team initiated a screening protocol for prostatitis that consisted of two tests: expressed prostatic secretion and post-prostate massage urine, also known as the voiding bottle 3, or VB3 test. Screening was performed for 122 men with PSA of 4.1 ng/mL to 29 ng/mL and no evidence of acute urinary tract infection.

Forty-two percent of the men had positive laboratory results for prostatitis, although most had negative VB3 cultures. These men received antibiotics for 4 weeks followed by reassessment, while men with negative laboratory tests underwent biopsy. After treatment, 22 of the 51 men with signs of prostatitis had normalized PSA levels, while the PSA remained elevated in 29. Of these 29 men, follow-up biopsy revealed cancer in 9 patients.

Overall, the screening protocol reduced the number of biopsies performed by 18%, and increased the positive predictive value of PSA for prostate cancer "substantially," from 37% to 51%. Moreover, all of the men who did not undergo biopsy after treatment for prostatitis had "continued normal or stable PSA" at last follow-up.

J Urol 2000;184:1550-1553.

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Here is a recent study and a long article on prostatitis:

New Study Offers Hope for Chronic Prostatitis Treatment

January 13, 2000

Urology/MedscapeWire

More than 80% of chronic prostatitis patients who took a proprietary formulation of quercetin, a natural dietary supplement, significantly reduced pain and improved their quality of life, according to a new study published in the December issue of Urology. This marks the first time any tested therapy for chronic prostatitis has produced such demonstrative results.

The randomized, double-blind, placebo-controlled study, conducted by researchers at the Institute for Male Urology in Encino, Calif, found that 82% of patients who received Prosta-Q, a specially formulated blend of the bioflavonoid quercetin, recorded at least a 25% improvement in the National Institutes of Health pain and quality of life symptom score.

"These impressive findings should offer hope to the millions of men who suffer from this poorly understood and painful condition, as it provides a new option for doctors who've been frustrated by limited treatment choices," said lead researcher Daniel A. Shoskes, MD, a renal transplant specialist and associate professor of urology at the University of California Los Angeles School of Medicine. "Importantly, all of these men had failed multiple courses of antibiotics and other therapies before participating in this study."

Nonbacterial chronic prostatitis is an inflammation of the prostate gland that affects an estimated 30 million men in the United States. Its chief symptom is chronic urogenital pain, and it is believed to impact quality of life as dramatically as myocardial infarction and Crohn disease. Its etiology is poorly understood, and standard antibiotic treatments have offered limited success.

"Chronic prostatitis is an enormous problem in our country and around the world," Dr. Shoskes said. "It's one of the most common reasons why men visit urologists, and it's one of the most discouraging conditions doctors face, because often times there's very little we can do to alleviate the pain."

Quercetin is a natural substance, known as a bioflavonoid, that's found in red wine, onions, and green tea. It's been clinically shown to have antioxidant, anti-inflammatory and antimicrobial properties. Dr. Shoskes, who had successfully used quercetin in preclinical studies with kidney transplants, decided to test the therapy on prostatitis patients, since an inflammatory cause is strongly suspected. Early results were disappointing because of quercetin's low absorption rate. Dr. Shoskes and fellow researchers then reformulated the product to increase quercetin's absorption into the system. Results with the new Prosta-Q formulation were so convincing, the researchers concluded the study early.

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Post to PHML on October 28, 2000 by Don Cooley

To All

Here is a long article on prostatitis. I left out the tables and the references to the tables. If you are interested you can use the URL below to see the whole article. You may have to join but that should be no problem.

One of the interesting things that is said is the following: >>Antibiotic therapy for 4 to 12 weeks is the major treatment, although eradication of bacteria occurs only 60% to 80% of the time and may not last 6 months.

I am continuing saying that you have to take Cipro for 5 or 6 weeks and I see posts that doctors have given the patient 2 weeks. Even 6 weeks may not be enough. On top of that it may not last 6 months. This would mean that you might want to consider taking some anti-prostatitis action whenever you are going to take your PSA. Notice there is some discussion about Cox-2 and NSAID's.

Remember that we have seen a post of a man with a PSA of 64 and after he was treated for prostatitis it came down to only 7.

You may want to print this and take it to your doctor if you think you have a problem.

Don

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NOTE: To view the article with Web enhancements, go to:

http://www.medscape.com/SCP/IIU/2000/v13.n05a/u135A.03.nick/u135A.03.nick-01.html

Chronic Prostatitis: Current Concepts and Antimicrobial Therapy

J. Curtis Nickel, MD, Queen's University, Kingston, Ontario et al

Abstract

Prostatitis accounts for 1% of visits to family physicians and 8% of visits to urologists and affects almost 10% of the adult male population. The International Prostatitis Collaborative Network has devised and validated a clinically useful classification of prostatitis that urologists and primary care clinicians will find helpful. According to this schema, chronic bacterial prostatitis is clearly an infectious disease, and patients with chronic prostatitis associated with chronic pelvic pain syndrome (CPPS) can have either inflammatory or noninflammatory disease. Chronic bacterial prostatitis is uncommon; chronic prostatitis with CPPS is extremely common. Antibiotic therapy is indicated in management of chronic bacterial prostatitis and inflammatory CPPS. Fluoroquinolones have been shown to be safe and effective, have good prostate tissue penetration and favorable pharmacodynamic properties, and achieve high clinical and bacteriologic cure rates, even in men with prostatitis refractory to other antibiotic therapies.

Introduction

Prostatitis, which remains among the last major frontiers in urology, is a common reason for office visits in primary care and urology. Although the diagnosis is generally based on the history and physical examination, no single clinical finding or laboratory result is definitive. Understanding of the pathophysiology of this prevalent condition is limited, even with respect to the significance of bacterial involvement. Similarly, optimal treatment for most men with prostatitis remains to be defined. Nevertheless, antibiotic therapy is a mainstay of treatment and is generally perceived to be beneficial for patients with acute and chronic bacterial prostatitis, inflammatory forms of chronic prostatitis, and chronic pelvic pain syndrome (CPPS). This review will outline the important concepts in the current thinking about diagnosis, classification, and therapy in prostatitis and will present more detailed information about antibiotic therapy for patients with bacterial prostatitis. It will also explain the rationale for and clinical use of the Chronic Prostatitis Symptom Index (CPSI), a tool for standardizing how patients describe the clinical features and the severity of their disease.

Scope of the Problem: Epidemiologic Perspective and Quality of Life

Prostatitis, especially in its chronic forms, is widespread among men and becomes increasingly common with advancing age.

Incidence and Prevalence of Prostatitis

In the early 1990s (1990-1994), there were as many office visits for prostatitis as there were for benign prostatic hyperplasia (BPH) or prostate cancer -- more than 2 million annually.[1] These accounted for 1% of all visits to family physicians and 8% of visits to urologists, and the numbers continue to rise.[2] Overall, the prevalence of prostatitis is between 5% and 9% of the male population aged 18 years and older.[3,4] In Wisconsin, a urologist sees an average of 173 patients with prostatitis each year.[5] In Canada, the average urologist sees 262 patients annually for prostatitis, and 38% of them have newly diagnosed disease.[6]

Impact on Quality of Life

Prostatitis is a debilitating disease that affects men of all ages. Its effect on quality of life has been examined using various measures. The quality of life for a patient with chronic prostatitis is similar to that experienced by patients with acute myocardial infarction, unstable angina, or active Crohn disease.[7,8]

Diagnosing Chronic Prostatitis: Classification, Etiology, the Symptom Index, and Diagnosis The clinical assessment of the patient with chronic prostatitis comprises symptoms, parameters of inflammation (primarily, the white blood cell count), and the presence or absence of bacteria. Bacteria, which may be uropathogens, fecal flora, or commensal organisms, are absent (or, at least, cannot be isolated) in approximately 95% of patients with chronic prostatitis. These patients have been said to have chronic nonbacterial prostatitis or prostatodynia. New understanding, however, suggests that many of these patients may not have prostate disease. The traditional classification of prostatitis, which stipulated acute bacterial prostatitis, chronic bacterial prostatitis, nonbacterial or abacterial prostatitis, and prostatodynia, has been difficult for clinicians to use.[9] It is therefore giving way to a new classification that is being developed and validated by the International Prostatitis Collaborative Network (IPCN).[10]

Classification of Prostatitis

Under the auspices of the NIH, the IPCN convened consensus conferences in 1995 and 1998 for the purpose of establishing definitions and classifications of prostatitis syndromes that reflect clinical reality (Table I).[10-12] The definitions and diagnostic criteria have already been found to be useful in practice and will serve as the framework for further studies on the etiology and treatment of prostatitis. Acute bacterial prostatitis (Category I), an acute infection of the prostate gland, is manifested by signs and symptoms of acute urinary tract infection (UTI). Most patients have urinary frequency and urgency; most also have fever, malaise, and myalgias that suggest systemic infection. Bacteriuria and pyuria are caused by standard uropathogens, especially Escherichia coli. Acute bacterial prostatitis is easily recognized, readily treated, and essentially unrelated to the other categories of prostatitis.

Chronic bacterial prostatitis (Category II) is associated with recurrent episodes of UTI caused by the same organism (usually E coli, but occasionally other gram-negative organisms or enterococci). This is a well-defined infectious disease of the prostate. That the prostate gland is the focus of infection may be demonstrated by lower urinary tract cultures of prostate-specific specimens (ie, expressed prostatic secretions [EPS], postprostatic massage urine, or semen) obtained between episodes of symptomatic bacteriuria. Chronic bacterial prostatitis is associated with ejaculate infection (bacteriospermia) and epididymitis, and the pH of the EPS is usually increased.[13]

1. Bacteriospermia in chronic bacterial prostatitis. In a study of more than 300 men with prostatitis, almost half of those with Category II disease had bacteriospermia; a much smaller proportion of men with Category IIIA or IIIB disease or who were healthy control subjects were bacteriospermic. Bacteriospermia was defined as greater than 103 colony-forming units/mL. Eradication of bacteriospermia typically follows effective antimicrobial therapy. (Based on data from Weidner W et al. Arch Androl. 1991.[13])

Acute and chronic bacterial prostatitis, while well understood, are uncommon. In fact, chronic bacterial prostatitis is difficult to find, even in a symptomatic population. In 1 study, only 7% of 656 patients seen in a urology clinic for evaluation of prostatitis symptoms had bacteriologically proven Category II disease.[14]

Chronic prostatitis associated with CPPS (Category III) is the new term applied to patients with symptomatic prostatitis of nonbacterial origin and reflects the fact that other organs may be contributing to symptoms. These patients, who represent 90% to 95% of men with nonbacterial prostatitis, do not have active urethritis, urogenital cancer, urinary tract disease, functionally significant urethral stricture, or neurologic disease involving the bladder. In patients with inflammatory CPPS, leukocytes are present in EPS, postprostatic massage urine, or semen. Those with noninflammatory CPPS do not have evidence of inflammation. Preliminary data suggest that different therapeutic algorithms are appropriate for inflammatory and noninflammatory CPPS.

Asymptomatic inflammatory prostatitis (Category IV) is diagnosed when there is evidence of infection or inflammation in the absence of a history of genitourinary pain. This pertains to 95% of men with BPH, 90% of men with prostate cancer, and 40% of men with infertility and is usually discovered incidentally during investigation of the genitourinary tract for other reasons. For example, among men with elevated prostate-specific antigen (PSA) levels, it is the second most frequently made diagnosis; cancer is the first.

Causes of Chronic Prostatitis and CPPS

Putative causes of chronic nonbacterial prostatitis and CPPS are numerous (Table II). A combination of an anatomic abnormality in the outflow tract and intraprostatic ductal reflux is believed to set the stage for peripheral prostatic irritation. Examples of such anatomic abnormalities include bladder neck-sphincter dyssynergia or other reasons for dysfunctional high-pressure voiding. Alternatively, a microorganism-based etiology may be postulated (Table III). Although, traditionally, it had been thought that lactobacilli, diphtheroids, and Corynebacterium species were not pathogenic in the prostate, evidence may link these organisms to inflammatory Category III disease (Category IIIA). In addition, coagulase-negative Staphylococcus, Chlamydia species, Ureaplasma species, and anaerobes have been localized to the prostate, and it is not known whether these are "innocent bystanders" or offending organisms. Data from several centers also point to the presence of a pathogenic microorganism that cannot be cultured using existing microbiologic techniques -- a story that suggests an analogy to the recently revealed role of Helicobacter pylori in peptic ulcer disease.

Other explanations that have been invoked include autoimmune mechanisms, chemical reactions (such as reflux of Tamm-Horsfall mucoprotein or urate into the prostatic ducts), and neuropathic processes and neurogenic inflammation in the perineum and pelvis. Some believe that prostatitis is nothing more than interstitial cystitis of the prostate, but this begs the question of what caused the cystitis in the first place.

Development and Use of the NIH-CPSI

The NIH-CPSI, a reliable, psychometrically robust, highly discriminative, comprehensive index has recently been published by the Chronic Prostatitis Collaborative Research Network (Figure 2).[15] The NIH-CPSI, which is intended for clinical practice settings as well as research protocols, is easily understood by patients as well as physicians and other health professionals. It has been reported on in at least 3 clinical trials and is being used in at least 6 ongoing randomized, controlled trials (evaluating cyclooxygenase [COX]-2 inhibitors, pentosan polysulfate, 5-a reductase inhibitors, phytotherapy, a-blockers, and microwave thermotherapy).

This standardized symptom index was developed from a structured literature review and focus groups of patients. An initial 55-question cognitive test was condensed into a 21-item draft that was reviewed by an expert panel and given formal validation by more than 500 patients, some of whom had prostatitis and others, with BPH or no prostate problems, who served as controls.

The final result was a simple survey tool that contained 9 questions and that required no more than 5 minutes to complete. The most important domains pertained to pain (location, severity, frequency), the nature of voiding (irritative and obstructive symptoms), and the impact of prostatitis on quality of life. For the majority of patients, severity of pain was twice as important as frequency of pain. The quality-of-life assessment correlated extremely well with results of the SF-36 health survey in patients with prostatitis.

Cost-Effective Screening and Diagnosis

The clinical diagnosis of chronic prostatitis is usually predicated on a 3-month history of genitourinary pain. The "gold standard" for diagnosis, the Meares-Stamey segmented quantitative culture technique,[16] is used by only a small minority of practicing urologists and a vanishingly small number of primary care physicians. Diagnostic efficiency may be enhanced cost-effectively, however, by a simple screening procedure in which urine obtained before and after prostatic massage is cultured and examined microscopically.[17] This is known as the Pre- and Post-Massage Test or, more colloquially, as "the 2-glass test." Patients who do not have clinical urethritis (itchiness, dysuria, or urethral discharge) can be stratified into Category II, Category IIIA, or Category IIIB with an accuracy exceeding 90% simply on the basis of urinary white blood cell count and culture results (Table IV). Diagnosis of chronic bacterial prostatitis (Category II), in particular, requires that the specimen be examined before and after prostatic massage to demonstrate that the bacterial count has increased after massage.

Therapy for Prostatitis: Overview and Outline of Options by Category In North America, antibiotics have been virtually de rigueur. Currently, almost all patients who receive a diagnosis of chronic prostatitis are treated with at least 1 course of antibiotics.[5,6,18] This is the case regardless of what the prostate-specific specimen showed and even when no such specimen was examined. As urologists, we should strive to do better by providing more specific therapy, treating only when indicated, and obtaining specimens to guide therapy when appropriate.

Until recently, evaluation of therapies for prostatitis has been hindered because studies have been short-term and small. There have been few randomized, placebo-controlled trials to date. Inclusion and exclusion criteria and outcomes parameters have been poorly defined or not comparable between studies. Currently, however, 6 randomized, controlled trials are under way in which the same inclusion, exclusion, and outcomes criteria are being used. Until the results of these trials are reported, there are a number of standard practices available (Table I).

Category I

Antibiotics are given, initially intravenously, then as culture-directed oral therapy. This is analogous to therapy for acute pyelonephritis, except that many patients require urethral or suprapubic catheterization. If therapeutic response is less than anticipated, an abscess should be considered; treatment is transurethral drainage and antibiotics.

Category II

Antibiotic therapy for 4 to 12 weeks is the major treatment, although eradication of bacteria occurs only 60% to 80% of the time and may not last 6 months. Moreover, eradication is not always associated with relief of symptoms. Fluoroquinolones provide optimal therapy. Prophylactic antibiotic therapy may be given for recurrent disease. Suppressive antibiotic therapy, possibly with prostatic massage or surgery, is appropriate when prostatitis is refractory to cure.

Category IIIA

Between 40% and 50% of patients with inflammatory CPPS respond to antibiotic therapy, and a 2- to 4-week therapeutic trial of antibiotics is recommended by the European Consensus Group on Prostatitis.[19] The justification is observed efficacy, and the mechanism is not known. Prostatic massage may enhance efficacy. a-Adrenergic blockade may have a role. Only phenoxybenzamine hydrochloride has been shown to be effective, compared with placebo, but orthostatic hypotension is significant at the required dosage.[20] More selective a-blocking agents, such as doxazosin mesylate, tamsulosin hydrochloride, and terazosin, may be beneficial.

A randomized controlled trial is currently under way to evaluate the new NSAIDs that selectively inhibit the COX-2 pathway. Small trials have suggested that finasteride or phytotherapy is more effective than placebo. Pentosan polysulfate, which is sometimes effective in interstitial cystitis, may provide relief. Transurethral microwave thermotherapy may also be tried. Surgery is inappropriate unless a specific indication (eg, bladder neck obstruction) is discovered.

Category IIIB

Few randomized, controlled trials support the use of any therapeutic modality. Experiences with a-blockade, analgesics, amitriptyline, muscle relaxants, biofeedback, physical therapy, lifestyle change, and supportive therapy are all anecdotal. A review of the literature and extensive personal experience suggest that muscle relaxants (a-blockers, diazepam) and various physical therapies (biofeedback) ameliorate the symptoms in many patients in this category.[21]

Category IV

No intervention is indicated because patients are asymptomatic. Exceptions to this rule may be made when the PSA level is elevated, the patient is infertile, or endoscopy or surgery is required (in which case, antibiotic prophylaxis is appropriate).

Therapy for Chronic Bacterial Prostatitis: Role of Fluoroquinolones The objectives of therapy for chronic bacterial prostatitis are to eradicate uropathogenic microorganisms, to normalize parameters of inflammation, and to relieve symptoms. The mainstay of treatment is antibiotic therapy. A large body of data supports the use of fluoroquinolones.[22]

Fluoroquinolones, such as ciprofloxacin, possess pharmacodynamic properties that are favorable for the treatment of bacterial prostatitis, including excellent penetration of the prostate gland, good bioavailability, and equivalence between oral and parenteral formulations of the same drug.[22,23] Clinical experience supports the statement that they are able to eradicate gram-negative bacteria from the prostate gland and from prostatic secretions in a high percentage of patients and for long periods.

Clinical Trials of Fluoroquinolones in Chronic Bacterial Prostatitis Trials with ciprofloxacin, norfloxacin, and ofloxacin yield similar results in men with chronic bacterial prostatitis (Table V). The cure rate does not appear to depend on the specific fluoroquinolone used. Schaeffer and Darras[24] evaluated the efficacy of a 28-day course of norfloxacin (400 mg bid) in 15 men whose chronic bacterial prostatitis was refractory to therapy with trimethoprim-sulfamethoxazole (TMP-SMX), carbenicillin, or both. The cure rate was 64% in 14 patients followed at least 6 months (the fifteenth patient had sterile post-treatment prostatic fluid cultures but was lost to follow-up). The cure rate was 75% in patients infected with E coli and 60% among patients with prostatic calculi. Norfloxacin resistance did not develop. In another study, ofloxacin, given for 14 days at a dosage of 400 mg/d, yielded a cure rate of 67%.[25]

Similar results have been obtained with ciprofloxacin in patients with chronic bacterial prostatitis, including those whose infection was refractory to therapy with TMP-SMX. Weidner and Schiefer[26] achieved eradication of E coli in 70% of patients and eradication of other pathogens in 40% of patients with a 28-day course of ciprofloxacin (500 mg bid). Patients had been symptomatic for at least 1 year and had not improved after 6-week courses of TMP-SMX or TMP. In a second study, Weidner and associates[27] found that a 28-day course of ciprofloxacin (500 mg bid) led to a 63% bacteriologic and clinical cure rate through a median follow-up of 30 months in men with refractory chronic bacterial prostatitis caused by E coli. A second course of ciprofloxacin was curative in another 13% of the patients.

Summary of Recent Ciprofloxacin Therapy Trials in Chronic Bacterial Prostatitis In studies at the Justus-Liebig University, Giessen, Germany, ciprofloxacin achieved a bacteriologic cure rate of up to 92% at 3-month follow-up and between 70% and 80% at 12-month and 24-month follow-up.[28] Therapy was given for 28 days at a dosage of 500 mg bid. Following eradication of E coli, the pH of the EPS decreased from 7.95 to 7.35, and the rate of bacteriospermia decreased from 95.5% before therapy to 27.3% 6 months after therapy. Naber and colleagues[29] demonstrated the safety and efficacy of ciprofloxain therapy in 65 men with symptomatic bacterial prostatitis. After 28 days of therapy, at a dosage of 500 mg bid, their study achieved the following benchmarks: 88.9% bacteriologic cure rate at 1-month follow-up, 98.1% clinical response rate at 1-month follow-up, 82.1% bacteriologic cure rate at 3-month follow-up, and 59.1% bacteriologic cure rate at 9-month follow-up. At least 1 adverse event was reported in 19 patients, but premature discontinuation of therapy was required in only 2 patients.

Conclusions

Prostatitis is prevalent and debilitating. Acute bacterial prostatitis (Category I prostatitis) is readily identified and amenable to treatment with antibiotics. Chronic bacterial prostatitis (Category II prostatitis), an infectious disease usually caused by E coli and associated with recurrent UTI and bacteriospermia, is uncommon but readily treatable with antibiotics, especially fluoroquinolones. Chronic prostatitis associated with CPPS (Category III prostatitis) accounts for most patients with prostatitis, and may be inflammatory or noninflammatory.

Almost 50% of men with inflammatory CPPS (Category IIIA prostatitis) benefit from antibiotic therapy, even though no evidence of bacteria can be found. No treatment for noninflammatory CPPS (Category IIIB prostatitis) has yet been supported by data from randomized, controlled trials. Asymptomatic inflammatory prostatitis (Category IV prostatitis) does not usually require intervention.

Fluoroquinolones are safe and effective in managing chronic bacterial prostatitis, because they have excellent pharmacodynamic properties, good prostate tissue penetration, high bioavailability, equivalence between oral and parenteral forms, and little proclivity for promoting bacterial resistance. Results with ciprofloxacin, norfloxacin, and ofloxacin are similar in men with chronic bacterial prostatitis refractory to treatment with TMP-SMX or carbenicillin.

References removed!

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FAIR USE NOTICE:

This document contains copyrighted material whose use has not been specifically authorized by the copyright owners. I believe that this not-for-profit, educational use on the web, via the Prostate-Help web sites and mailing lists, constitutes a fair use of the copyrighted material (as provided for in section 107 of the US Copyright Law). If you wish to use this copyrighted material for purposes of your own that go beyond fair use, you must obtain permission from the copyright owner.

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Overview Summary Statement

Urology; Volume 60 , Issue 6 (Supplement 0) , Pages 1-4

Overview summary statement

Anthony J. Schaeffer * a , Nand S. Datta b , Jackson E. Fowler Jr c , John N. Krieger d , Mark S. Litwin e , Robert B. Nadler a , J.Curtis Nickel f , Michel A. Pontari g , Daniel A. Shoskes h , Scott I. Zeitlin i and Carol Hart j

Abstract

Members of the Chronic Prostatitis Collaborative Research Network (CPCRN) met in a 1-day symposium to review recent findings and to debate unanswered issues in the diagnosis and management of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). The meeting was focused on producing an overview summary statement that would, as nearly as possible, represent the consensus views of the attendees. As discussed below, the participants agreed that a history, physical examination, and urinalysis/urine culture are mandatory for the evaluation of all patients presenting with CP/CPPS, with other assessments categorized as recommended or optional, depending on the history and physical findings. Observations and suggestions regarding first- and second-line therapies are also offered, with the recognition that randomized, placebo-controlled trials to guide selection of therapies for chronic nonbacterial prostatitis are currently lacking.

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The Chronic Prostatitis Collaborative Research Network (CPCRN) was formed in 1997 by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health (NIH) to conduct research in chronic prostatitis (CP). The Network launched a prospective longitudinal Chronic Prostatitis Cohort Study, 1 which is collecting data on the natural treated history of the disorder, as well as outcomes of investigational treatments. The Network also developed the first validated instrument for assessing symptom severity in CP, the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI). 2

Members of the CPCRN met in a 1-day symposium held in Chantilly, Virginia, March 26, 2002, to present and discuss updated information from ongoing trials, including the Chronic Prostatitis Cohort Study, as well as results of recent pilot studies examining a number of pharmacologic and nonpharmacologic therapies. The symposium format combined brief presentations with extended periods of open discussion, which are included in abridged form in this supplement to Urology.

In the discussions, symposium participants focused on applying the presented findings to the development of a working consensus on the diagnosis and appropriate management of chronic nonbacterial prostatitis, and to identifying unresolved issues that should be the focus of future investigations. Although much has been learned in the 5 years since the CPCRN was formed, symposium participants emphasized that the information available does not allow the development of evidence-based guidelines or recommendations. This summary report is instead offered as a clinically useful update on diagnosis and management of chronic nonbacterial prostatitis.

Diagnostic criteria

In a 1995 NIDDK-sponsored workshop on CP, the decision was made to characterize chronic nonbacterial prostatitis as a chronic pelvic pain syndrome (CPPS), in recognition that pelvic pain complaints were the most characteristic symptoms and that the role of the prostate in producing symptoms is in fact still unknown. This entity, chronic nonbacterial prostatitis/chronic pelvic pain syndrome (CP/CPPS), or category III prostatitis, was further categorized as having 2 subclasses, inflammatory and noninflammatory, based on the presence or absence of leukocytes in the expressed prostatic secretions, post–prostate massage urine, and semen. 3

Given the limited data on etiology and mechanisms of category III prostatitis, CP/CPPS cannot be rigidly defined. Differing criteria can be applied to make the diagnostic category more or less inclusive. Symposium participants suggested that CP/CPPS could be broadly defined as the presence of characteristic symptoms of discomfort or pain in the pelvic region for a period ?3 months within the past 6 months. The NIH Chronic Prostatitis Symptom Index (NIH-CPSI) is an excellent tool for qualifying the severity of the patient’s symptoms. CP/CPPS is primarily a diagnosis of exclusion, with diagnostic assessment focused on detecting any underlying abnormalities or primary disorders that may be producing the pelvic pain and associated symptoms.

Ongoing research is directed at identifying laboratory markers that might serve to corroborate the patient’s complaint and to differentiate any subgroups that might differ in disease mechanisms and treatment response. Although some preliminary studies have identified inflammatory markers of potential importance, there are as yet no objective measures that can be applied for diagnosis or monitoring. In fact, as discussed below, recent data now available from the Chronic Prostatitis Cohort Study 4 suggest that the leukocyte counts used to distinguish subcategories of CP/CPPS may have limited clinical utility.

Diagnostic assessment

Recommendations for the evaluation of patients presenting with CP are presented in the summary by Nickel contained in these proceedings. Briefly, symposium participants considered that a history, physical examination, and urinalysis/urine culture are mandatory for the evaluation of all patients presenting with CP/CPPS.

Participants felt that the NIH-CPSI (reproduced as Table I in the summary by Litwin) has value for the diagnosis and follow-up treatment of patients with CP, although it was developed primarily as a research instrument and its clinical utility has not been fully evaluated. Nonetheless, it has been used for this purpose by practicing urologists. Lower urinary tract localization studies have long been considered by researchers, if not by clinicians, to be necessary for the work-up of all patients presenting with CP. In the Chronic Prostatitis Cohort study, 8% of the patients had positive localization studies for established urinary pathogens, and >60% had localizing cultures for any type of bacteria, suggesting a possible bacterial cause for their pain and the potential for benefit from antimicrobial therapy. Symposium participants felt that there was little evidence that the results provided useful guidance to the management of CP/CPPS, and therefore, localization studies were considered recommended, rather than mandatory, in the initial assessment of patients presenting with CP/CPPS. However, such studies may prove very helpful for patients with a history of urinary tract infection (bacteriuria, possible category II), where results may guide therapeutic decisions.

There is insufficient evidence to recommend urine cytology for all patients presenting with CP/CPPS. However, urine cytology is mandatory for patients with microscopic hematuria. It is recommended for the evaluation of patients with irritative voiding symptoms (ie, suprapubic pain or dysuria). Cystoscopy can identify potentially important and treatable lower urinary tract abnormalities. Indications for cystoscopy in patients include hematuria, suspicious cytology, abnormal urodynamics, and irritative or obstructive voiding symptoms.

Significance of leukocytes and the role of inflammation in chronic prostatitis/chronic pelvic pain syndrome

The role of inflammation in the onset and perpetuation of CP/CPPS is at the present time unknown. Some patients may have inflammation as the cause of their symptoms. However, white blood cells in the fluids (semen, post–prostate massage urine or expressed prostatic secretions) do not appear to be the optimal marker of inflammation, and the current categorization of CP/CPPS as inflammatory or noninflammatory based on leukocyte counts appears to offer little clinically useful information. As the Cohort Study has shown, 4 leukocyte counts do not correlate with symptom severity, nor do they appear to have great value in selecting treatment or predicting treatment response. However, there is preliminary evidence suggesting that other inflammatory markers, in particular, interleukin-1? and tumor necrosis factor-?, may be predictive. Several studies that have looked at markers of oxidative stress and cytokine levels have found a correlation with symptoms and/or response to treatment. 5–8 Further investigation in this area may lead to the development of clinically useful assays as well as provide insights into the mechanisms underlying CP/CPPS.

Significance of bacterial presence and the role of infection in chronic prostatitis/chronic pelvic pain syndrome

Current evidence does not establish that bacteria are the cause of CP/CPPS. However, recent findings indicate that many patients with CP/CPPS have molecular markers indicative of past or present colonization or infection, despite repeated negative cultures. 9 These organisms may be pathogens that cannot be isolated from the fluids available for testing or that cannot be cultured on conventional media. Another hypothesis is that bacterial presence may be the stimulus for an immune response that results in inflammation and pain.

The symposium participants concluded that inflammation and bacterial presence may be important in the etiology of CP/CPPS but cannot be adequately assessed with current clinically available methods.

Treatment of chronic prostatitis

Antimicrobial therapy must be considered an unproven therapy for the treatment of CP/CPPS, because to date, there are no published randomized placebo-controlled trials to establish its efficacy. Nonetheless, both clinical experience and a recent open-label study indicate that antimicrobial therapy often provides some degree of symptom relief in CP, regardless of disease category. 10

The observed benefit may ultimately prove to be a placebo effect, but it is also possible that antimicrobial agents are effective against organisms that cannot be isolated or cultured by currently available clinical microbiology techniques. It is also possible that the anti-inflammatory effects of the antimicrobials may account for part or all of the symptom relief reported by patients. Given the absence of proven therapies in CP/CPPS, it is reasonable to offer patients a single 4- to 6-week trial of antimicrobial therapy. If the agent does not provide at least temporary symptom relief, this approach should not be repeated.

?-Blockers, such as terazosin and alfuzosin, are commonly used to treat CP/CPPS, although, again, there are few well-designed studies to evaluate their efficacy. A number of observations of the physiology and pathophysiology of the lower urinary tract have been adduced to support the choice of ?-blockers for the management of CP/CPPS, as summarized by Datta later in this supplement. For now, ?-blockers are a reasonable option for second-line therapy, particularly if flow rate and residual urine determinations or urodynamic studies suggest lower urinary tract dysfunction.

Anti-inflammatory agents have potential, although as-yet unproven efficacy. The only randomized placebo-controlled trial of this class of medication found a statistically significant response for 50 mg/day rofecoxib, a cyclooxygenase-2 inhibitor, on some but not all endpoints evaluated. 11 At the present time, a short course of a nonsteroidal anti-inflammatory agent is considered to be a reasonable treatment option, given the favorable adverse-effect profile, the promising results seen in small preliminary studies, and the increasing evidence that anti-inflammatory markers are elevated in CP/CPPS.

There are 2 other agents that may be exerting anti-inflammatory effects and that have shown efficacy in small placebo-controlled trials: pentosan polysulfate and finasteride. 12,13 These therapies mentioned above all merit further investigation in larger and longer duration trials.

Cernilton and quercetin are 2 herbal therapies that have shown benefit in small preliminary studies. Cernilton, a pollen extract, has been evaluated in an open-label study in selected patients. 14 Quercetin, a bioflavonoid found in red wine, onions, and other foods, was found effective in a small but well-designed placebo-controlled trial as well as a preliminary open-label study. 15,16 Other popular ”prostatic health“ supplements, including saw palmetto, stinging nettle, Pygeum africanum, and zinc, do not appear to be effective for CP/CPPS. Quercetin and Cernilton produce few if any adverse effects and may offer meaningful benefit to a substantial proportion of CP/CPPS patients.

Nonpharmacologic therapies for CP/CPPS include biofeedback and a number of heat modalities. Biofeedback has been studied only in a very small number of patients. However, approximately 33% of patients in a treatment-resistant population had meaningful improvement after an 11-week program of biofeedback-based pelvic floor training. 17 Where available, biofeedback can be considered for treatment-resistant patients in whom flow rate and residual urine determination and/or urodynamic studies suggest voiding dysfunction.

A number of thermal therapies for CP/CPPS have been tried, but differences in patient selection, modality, delivery, achieved temperatures, and outcome measures render it difficult or impossible to compare reports to evaluate the overall success of this approach. Because of the significant morbidity associated with these therapies, they should probably be reserved for treatment-resistant patients whose quality of life is severely affected by the disorder.

Future clinical trials

The uncertainty about the etiology, mechanisms, and treatment of CP/CPPS can be discouraging to both patients and clinicians. Nonetheless, significant progress has been made in the last few years in the understanding and management of this disorder. The many small preliminary studies summarized throughout these proceedings suggest—if they cannot demonstrate—that there are a number of promising therapies that can be tried, most with quite tolerable adverse-effect profiles.

Importantly, well-designed studies are now in various stages of planning, recruitment, and data analysis. Already the Chronic Prostatitis Cohort Study is providing abundant demographic and epidemiologic data 1 that may aid in diagnosis and prognosis, as well as provide useful leads for investigations into the etiology of CP/CPPS. Continued follow-up investigation will likely yield information for use in planning clinical trials, perhaps helping to identify subgroups of patients with higher response rates to particular therapies.

The symposium closed with a discussion of what new trials should be instituted. Among the areas identified as deserving further investigation were (1) larger placebo-controlled studies of anti-inflammatory agents; (2) larger-scale phytotherapeutic trials; (3) a well-designed trial of prostatic massage; (4) development and study of a more cost-effective approach for biofeedback training; and (5) a multicenter thermal therapy trial, using a standardized approach, validated outcome instruments, and a sham therapy control group.

CP/CPPS is now achieving greater recognition as a significant disorder. As basic and clinical investigations into the pathophysiology and treatment of CP/CPPS continue, patients and clinicians can confidently expect more efficacious and more evidenced-based options for the management of this common and distressing disorder.

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References

1 Schaeffer A.J. , Landis J.R. and Knauss J.S. et al. (2002) Demographic and clinical characteristics of men with chronic prostatitis: the NIH Chronic Prostatitis Cohort (CPC) Study. J Urol 168:593-598 MEDLINE

2 Litwin M.S. (1994) Measuring health related quality of life in men with prostate cancer. J Urol 152:1882-1887 MEDLINE

3 Krieger J.N. , Nyberg L. Jr and Nickel J.C. (1999) NIH consensus definition and classification of prostatitis. JAMA 282:236-237 MEDLINE

4 Schaeffer A.J. , Knauss J.S. and Landis J.R. et al. (2002) Leukocyte and bacterial counts do not correlate with severity of symptoms in men with chronic prostatitis: the NIH Chronic Prostatitis Cohort (CPC) Study. J Urol 168:1048-1053 MEDLINE

5 Ruggieri M.R. , Braveraman A.S. and Pontari M.A. (2000) Biochemical markers for inflammation and glands that contribute to the semen in patients with chronic prostatitis/chronic pelvic pain syndrome. J Urol 163:26[abstract]

6 Nadler R.B. , Koch A.E. and Calhoun E.A. et al. (2000) IL-1beta and TNF-alpha in prostatic secretions are indicators in the evaluation of men with chronic prostatitis. J Urol 164:214-218 MEDLINE

7 Hochreiter W.W. , Nadler R.B. and Koch A.E. et al. (2000) Evaluation of the cytokines interleukin 8 and epithelial neutrophil activating peptide 78 as indicators of inflammation in prostatic secretions. Urology 56:1025-1029

8 Shahed A.R. and Shoskes D.A. (2000) Oxidative stress in prostatic fluid of patients with chronic pelvic pain syndrome: correlation with gram positive bacterial growth and treatment response. J Androl 21:669-675 MEDLINE

9 Krieger J.N. , Riley D.E. and Vesella R.L. et al. (2000) Bacterial DNA sequences in prostate tissue from patients with prostate cancer and chronic prostatitis. J Urol 164:1221-1228 MEDLINE

10 Nickel J.C. , Downey J. and Johnston B. et al. (2001) Predictors of patient response to antibiotic therapy for the chronic prostatitis/chronic pelvic pain syndrome: a prospective multicenter clinical trial. J Urol 165:1539-1544 MEDLINE

11 Nickel J.C. , Gittleman M. and Malek G. et al. (2001) Effect of rofecoxib in patients with chronic nonbacterial prostatitis: a placebo controlled pilot study. J Urol 165:27[abstract] MEDLINE

12 Nickel J.C. , Forrest J. and Tomera K.M. et al. (2002) Effects of pentosanpolysulfate sodium in men with chronic pelvic pain syndrome: a multicenter randomized placebo controlled study. J Urol 167: (suppl) 63[abstract]

13 Downey J. , Nickel J.C. and Pontari M.A. et al. (2002) Randomized placebo controlled multi-center pilot study to evaluate the safety and efficacy of finasteride in the treatment of male chronic pelvic pain syndrome: category IIIA CPPS (chronic nonbacterial prostatitis). J Urol 167: (suppl) 26[abstract]

14 Rugendorff E.W. , Weidner W. and Ebeling L. et al. (1993) Results of treatment with pollen extract (Cernilton N) in chronic prostatitis and prostatodynia. Br J Urol 71:433-438 MEDLINE

15 Shoskes D.A. , Zeitlin S.I. and Shahed A. et al. (1999) Quercetin in men with category III chronic prostatitis: a preliminary prospective, double-blind, placebo-controlled trial. Urology 54:960-963

16 Shoskes D. (1999) Use of the bioflavonoid quercetin in patients with long-standing chronic prostatitis. J Am Neutraceut Assoc 2:18-21

17 Clemens J.Q. , Nadler R.B. and Schaeffer A.J. et al. (2000) Biofeedback, pelvic floor re-education, and bladder training for male chronic pelvic pain syndrome. Urology 56:951-955

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Affiliations:

a Department of Urology, Northwestern University Medical School, Chicago, Illinois, USA. b Division of Urology, King/Drew Medical Center, Charles R. Drew University, Los Angeles, California, USA. c Division of Urology, University of Mississippi Medical Center, Jackson, Mississippi, USA. d Department of Urology, University of Washington, Seattle, Washington, USA. e David Geffen School of Medicine, University of California Los Angeles School of Public Health, Los Angeles, California, USA. f Department of Urology, Kingston General Hospital, Queen’s University, Kingston, Ontario, Canada. g Department of Urology, Temple University School of Medicine, Philadelphia, Pennsylvania, USA. h Cleveland Clinic Florida, Weston, Florida, USA. i Department of Urology, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, California, USA. j InforMEDical, Inc., Narberth, Pennsylvania, USA.

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* Reprint requests: Anthony J. Schaeffer, MD, Northwestern University Medical School, Department of Urology, 303 East Chicago Avenue, Tarry 11-715, Chicago, Illinois 60611-3008, USA.

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Copyright © 2002 Elsevier Science Inc. All rights reserved.

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September 21, 2008