Chronic Bacterial Prostatitis Treatment & Management

Updated: Jan 15, 2019
  • Author: Samantha D Kraemer, MD; Chief Editor: Edward David Kim, MD, FACS  more...
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Treatment

Approach Considerations

Antibiotics are the most common therapy used to treat chronic bacterial prostatitis (CBP). Eradication of bacteria is associated with clinical success in the short and long term with CBP caused by both traditional and nontraditional bacteria.

Studies have shown that patients with a recent diagnosis of prostatitis who are antibiotic-naive have an excellent symptomatic response, regardless of culture status. [34, 35] In contrast, men with chronic prostatitis or chronic pelvic pain syndrome (CPPS) of long duration who have been previously treated are not likely to have symptom improvement with a course of antibiotics, and therefore should not be given antibiotics. [1] Antibiotic therapy can be used in an attempt to cure CBP but relapses are common. CBP in men with prostatic calculi is more difficult to cure. 

Fluoroquinolones are the mainstay in the treatment of CBP. Fosfomycin has been shown to have good activity against extended-spectrum beta-lactamase producing organisms. Azithromycin may be more effective for Chlamydia infections. Most other antimicrobial agents are unlikely to eradicate the infection. 

Although bacteria are cultured in only 5%-10% of prostatitis cases, bacteria may still be the cause of the chronic prostatitis in many patients with the syndrome. Studies using extensive research methods (eg, reverse transcriptase polymerase chain reaction assay) show evidence of bacterial infection in some patients despite negative urine cultures. Negative culture results occur for various reasons, including insufficient sample volume, initiation of antibiotics prior to obtaining an expressed prostatic secretion sample, and the presence of fastidious organisms.

In such cases, patients often have improvement in symptoms with antibiotic treatment. Thus, if clinical evidence strongly suggests chronic prostatitis in a patient with negative cultures, a 2-week trial of antibiotics is worthwhile. If the symptoms improve, prescribe a complete course of antibiotics. 

In most cases, symptomatic treatment with analgesics and alpha blockers may be used to help alleviate symptoms. Sitz baths also may provide symptomatic improvement.

Surgery is usually not indicated for chronic prostatitis. However, in select situations when a patient has episodes of chronic prostatitis that improve with antibiotics but then recur, transurethral resection of the prostate (TURP) or transurethral vaporization of the prostate (TUVP) may remove a nidus of infection. This nidus may be in the form of prostatic stones. These stones are usually visible on transrectal ultrasonograms. [36]

Other therapies used to treat CPPS may provide symptomatic improvement for CBP but have not been studied extensively in the CBP population. These other therapies include the following [37, 1, 26, 29, 70]

  • Physiotherapy with myofascial release and paradoxical relaxation
  • Biofeedback, transcutaneous electrical nerve stimulation (TENS), acupuncture 
  • Medications for neuropathic pain (gabapentinoids, antidepressants) 
  • Psychotherapy
  • Neuromodulation procedures (spinal cord or sacral nerve root stimulation) 
  • Bladder retraining 
  • Therapeutic ejaculation 

A meta-analysis concluded that viewing chronic prostatitis/CPPS as a psycho-neuromuscular disorder driven by protective pelvic floor guarding and psychosocial stress, and treating with techniques such as myofascial trigger point release, biofeedback, and cognitive-behavioral therapy, can result in clinically significant improvement in symptoms. [69]

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Antimicrobial Therapy

The choice of antimicrobial is critical because the prostate has an epithelial lining and a pH gradient that inhibits antimicrobials from entering the prostatic acini. Ideal antibiotics have a higher dissociation constant to allow diffusion of their non-ionized components into the prostate. In addition, if the antibiotic has a basic pH, it can readily reach much higher concentrations in prostatic fluid than in the plasma because of the pH gradient. Agents able to reach sufficient concentrations in prostatic tissue include fluoroquinolones, macrolides, tetracyclines, and trimethoprim. 

The choice of antibiotics for treatment should also be guided by urine bacterial cultures and sensitivities. It is important to use an antibiotic with broad-spectrum coverage because many different bacteria have been isolated in the prostate, although gram-negative Enterobacteriaceae group are the most common. 

Antibiotic therapy begins with initial 4- to 6-week course. A second course of 4-6 weeks can be offered if a bacterial cause is confirmed or the first course resulted in a partial symptomatic response.

If bacterial cultures remain positive, longer treatment is necessary. The best results have been observed with a 12-week course of therapy, although maintaining patient compliance may be difficult with longer durations of treatment.

A second cycle of antibiotics can be considered if initial treatment fails, because according to some authors up to 20% of patients in whom initial treatment failed may be rescued by using a second cycle. [1] If the patient obtains no obvious symptomatic benefit from infection control or cultures are negative, repeated use of antibiotics should be avoided. [26]

Fluoroquinolones

The antibiotics of choice are the fluoroquinolones (eg, ciprofloxacin, levofloxacin, ofloxacin, moxifloxacin), due to their favorable pharmacokinetic properties and broad-spectrum activity. Fluoroquinolones have demonstrated high bactericidal activity against the Enterobacteriaceae group of bacteria and against Pseudomonas aeruginosa. They also have activity against chlamydial and gonococcal organisms. However, fluoroquinolones are generally ineffective against streptococci, enterococci, and anaerobes.

Reported microbiological eradication rates are 40%-70% for ciprofloxacin and 75% for levofloxacin. One comparative study of patients with CBP concluded that levofloxacin 500 mg once daily is as effective as ciprofloxacin 500 mg twice daily for 4 weeks [38] A similar study found that compared with ciprofloxacin, levofloxacin produced higher rates of bacterial clearance and clinical improvement, as well as lower rates of microbiological recurrence. [39]

In contrast, a systematic review of 18 studies reported no significant differences in clinical improvement, microbiological eradication, or rate of adverse effects among oral fluoroquinolones, including ciprofloxacin, levofloxacin, lomefloxacin, ofloxacin, and prulifloxacin. [40] The optimal duration of fluoroquinolone treatment for CBP caused by traditional organisms is not well studied and more research is needed optimize doses and lengths of antibiotics being prescribed. 

Fluoroquinolone therapy is not always feasible in patients with contraindications such as long QT syndrome or tendonitis. Reported resistance rates to fluoroquinolones in Enterobacteriaceae causing urinary tract or intra-abdominal infections have increased in previous years and exceed 50% in some parts of the world, especially Asia. In Europe and North America, resistance rates range from less than 10% in rural areas to more than 30% in sexual networks. [41]

National and international antibiotic stewardship practices have helped to lower the percentage of ciprofloxacin-resistant extended-spectrum β-lactamase (ESBL) Enterobacteriaceae in urinary isolates in both hospital and community settings. [42] Nevertheless, alternative antibiotics for treating CBP are needed. 

Trimethoprim/sulfamethoxazole

Trimethoprim/sulfamethoxazole (TMP/SMX) or even trimethoprim alone were widely used in the 1970s to 1990s. Eradication rates ranged from 0% to 67%, with most studies reporting rates of 30%-50% with a 4- to 6-week course of treatment. Longer duration of therapy, around 90 days, provides best clinical results. TMP/SMX does have good penetration into the prostate and activity against most relevant pathogens but resistance rates are high. It does not have activity against Pseudomonas,Chlamydia, or gonococci. Overall, TMP/SMX is less effective for bacterial eradication than fluoroquinolones. [1]

Azithromycin

Azithromycin, a macrolide antibiotic, has reported eradication rates of around 80%. [20] It has good penetration into the prostate and is active against gram-positive bacteria and Chlamydia. It should not be used as a first-line antibiotic but can be used when microbiological studies identify susceptible pathogens. For Chlamydia infections, azithromycin has been reported to be superior to ciprofloxacin with respect to clinical response and eradication rates. [40] Clarithromycin, another macrolide antibiotic, is equivalent to azithromycin in both clinical response and eradication rates. [40]

Fosfomycin

Fosfomycin achieves reasonable tissues levels in the prostate and should be considered in patients with multidrug-resistant gram-negative bacteria on cultures. Fosfomycin is more active in an acidic environment, so the alkaline pH seen during CBP may decrease its activity.

Case reports have documented successful use of fosfomycin for treatment of prostatitis caused by multidrug-resistant gram-negative bacilli. [43, 71] A single case report describes successful use of the combination of fosfomycin and doxycycline to treat persistent prostatitis from ESBL-positive Escherichia coli that was refractory to prolonged courses of fosfomycin alone. [44]

Los-Arcos et al reported on the use of fosfomycin-tromethamine in 15 patients with CBP (five with multi-drug–resistant Enterobacteriaceae [MDRE] infection) that had proved difficult to treat because of adverse effects or resistance to ciprofloxacin and cotrimoxazole. The patients received 3 g every 48-72 h for 6 weeks. After a median follow-up of 20 months, seven of the patients (47%) had clinical responses and eight (53%) had persistent microbiological eradication; four of the five patients with MDRE isolates achieved eradication. None of the patients experienced adverse effects. [45]

Other antibiotics 

Doxycycline, a tetracycline antibiotic, has good activity against Chlamydia and Mycoplasma but unreliable activity against Enterobacteriaceae and staphylococci and no activity against Pseudomonas. It has no conclusive role in the treatment of CBP. 

Carbenicillin may be effective for Enterobacteriaceae or Pseudomonas infections. Large-scale studies are not available. Other penicillin derivatives, while effective against gram-positive organisms, are generally ineffective in treating bacterial prostatitis because of poor prostate penetration.

Aminoglycoside antibiotics have been suggested as a possible alternative for CBP treatment. They are one of the recommended agents for treatment of acute bacterial prostatitis.

In a study of 78 men with fluoroquinolone-resistant CBP or contraindications to fluoroquinolone therapy, Vittorio et al reported that intramuscular netilmicin once daily for 4 weeks produced a 78.6% eradication rate and significant reductions in the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) score at 6-month and 12-month followup in those with eradicated infections. Genetic testing for deafness-predisposing mitochondrial mutations guided safer administration and overall therapy was well tolerated. [46] Further randomized controlled studies are needed to verify aminoglycosides as a therapeutic alternative. 

Ureaplasma infections can be treated with ofloxacin, minocycline, azithromycin, or doxycycline. Those agents all produce similar rates of clinical improvement and microbiological eradication and have similar toxicity profiles. [40]

Nanobacteria have been implicated in stone formation within the urinary tract, so eliminating them may improve to chronic prostatitis symptoms. Preliminary findings suggest that anti-nanobacterial therapy improves symptoms and decreases or eliminates prostatic calculi in patients with CPPS that is recalcitrant to standard therapy. Further investigation is needed. [47]

Suppressive antibiotics

Patients with persistent or recurrent infections, especially those who have symptom improvement while on antibiotics but who quickly have a recurrence after finishing a course of antibiotics, may benefit from suppressive therapy with low-dose daily prophylactic antibiotics. Clinical studies have not confirmed the value of suppressive therapy in this setting, but it is widely used. [1] Good choices are tetracycline, nitrofurantoin, nalidixic acid, cephalexin, and trimethoprim. Bacteria in CBP are usually sensitive strains, even after a number of antibiotic treatment regimens have been tried.

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Additional Treatments

In a meta-analysis of randomized, controlled trials of pharmacologic therapy for the treatment of chronic prostatitis and chronic pelvic pain syndrome, Anothaisintawee et al concluded that alpha blockers and antibiotics, as well as combinations of these therapies, appear to achieve the greatest improvement in NIH-CPSI scores (total, pain, voiding symptoms, and quality of life) compared with placebo. Anti-inflammatory therapies had a lesser, but measurable, benefit on selected outcomes; however, the investigators noted that sample sizes in many studies were small and that publication bias might have overestimated the benefits reported. [48]

Another systemic review and meta-analysis on therapuetic interventions for patients with chronic prostatitis and chronic pelvic pain syndrome, concluded that the macrolide antibiotic mepartricin, percutaneous tibial nerve stimulation, and triple therapy (with doxazosin, ibuprofen, and the muscle relaxant thiocolchicoside) resulted in both clinically and statistically significant improvements in total NIH-CPSI scores. But they did not find statistically or clinically significant reductions in NIH-CPSI with alpha blockers, antibiotics, or combinations of the two. [49] Many of these studies included mostly patients with CPPS (negative cultures), and therefore more studies with patients who have CBP are needed. 

Alpha blockers

Alpha-adrenergic antagonist medications include tamsulosin, alfuzosin, doxazosin, terazosin, and silodosin. The uroselective alpha blockers (tamsulosin, alfuzosin, and silodosin) have better adverse-effect profiles and should be first-line choices. The alpha blockers can help to decrease recurrences by diminishing urinary outflow obstruction due to prostate enlargement or congestion secondary to inflammation and improve urinary flow or diminish intraprostatic ductal reflux. 

These agents have provided significant symptom reduction and improvement in quality of life in patients with CBP, as well as those with CPPS. Ten randomized controlled studies evaluating alpha blockers in patients with prostatitis symptoms, mostly in men with CPPS, have been published, with eight of them reporting positive results, using the NIH-CPSI or other validated symptom-scoring tools.

Experts advise that alpha blockers should be considered as part of initial treatment of patients presenting with lower urinary tract symptoms (LUTS), although there is insufficient evidence to inform best practice with these medications. [26] Alpha blockers should be used as part of a multimodal approach to treatment in a newly diagnosed patient, but are not recommended as monotherapy, especially if the patient has previously been treated with alpha blockers. [1] If no relief of symptoms is achieved in 4-6 weeks then the treatment should be discontinued. 

Pain medications

Nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids should theoretically improve inflammation within the prostate to help reduce symptoms, and studies suggest that these agents may be useful as adjunctive therapy for patients with chronic prostatitis.

Cyclooxygenase-2 inhibitors (eg, rofecoxib, celecoxib), which are used for treating other chronic inflammatory conditions, have been used by urologists for prostatitis, with some anecdotal success reported. High-dose rofecoxib was shown to improve symptoms, but this drug has been withdrawn from the market. [26] Celecoxib has been shown to provide significant symptomatic improvement in patients with CPPS, in a dose-dependent fashion, but benefits are limited to therapy duration. [50, 51]

One meta-analysis reported that NSAIDs (rofecoxib, celecoxib, and a corticosteroid) are 80% more likely to achieve a favorable response, compared with placebo. [48] However, another meta-analysis of only rofecoxib and celecoxib found no significant difference in response to NSAIDs versus placebo. [49] Overall, high-dose long-duration therapy with cyclooxygenase-2 inhibitors is not recommended for CBP. 

Pregabalin, a neuropathic pain medication, has been suggested for use in chronic prostatitis and CPPS. In a randomized, double-blind, placebo-controlled trial of 218 men by Pontari et al, 47.2% of men who received pregabalin had a decrease in NIH-CPSI total score; however, the decrease was not statistically significant, and pregabalin was not superior to placebo. [52]

Opioid analgesics have not been evaluated in chronic prostatitis but are unlikely to provide clinical benefit and pose a high risk of addiction. 

5-alpha-reductase inhibitor

Treatment with 5-alpha-reductase inhibitors (eg, finasteride, dutasteride) has been shown to be effective in relieving symptoms of prostatitis. In the REDUCE study, which was originally designed to evaluate whether treatment with dutasteride decreased prostate cancer risk in men with an elevated PSA, long-term use of dutasteride significantly reduced prostatitis-like symptoms, compared with placebo. [53]

A randomized, placebo-controlled pilot study by Nickel et al suggested that some men with category IIIA CPPS experience symptomatic improvement with finasteride. However, these authors concluded that the results did not justify recommending finasteride as monotherapy, except for men who also have benign prostatic hyperplasia. [54]

Supplements

Saw palmetto, an herbal supplement well known as a treatment for prostatic enlargement, has also been used for prostatitis. [55]  Saw palmetto is hypothesized to act similarly to 5-alpha-reductase inhibitors.

Quercetin, a polyphenolic flavonoid with antioxidant properties found in green tea, onions, and oranges, has also has been shown to significantly decrease symptoms. [56]

While zinc supplements have been suggested as a medical therapy, clinical results have not been significant. A zinc-containing polypeptide called prostatic antibacterial factor (PAF) may be an important antimicrobial factor within the prostate.

Other treatment modalities 

The role of ejaculation in the treatment of chronic bacterial prostatitis (CBP) is unknown. One theory is that frequent ejaculation may help to clear prostatitic secretions, thereby allowing for quicker resolution. Instruct the patient to ejaculate a minimum of every 3 days, either through intercourse or masturbation, while on antibiotic therapy to help with drainage of the prostatic ducts.

A double-blind, randomized, placebo-controlled study in 60 consecutive patients with CPPS refractory to medical therapy found that transurethral intraprostatic injection of botulinum neurotoxin type A reduced pain and improved quality of life. By 6 months after treatment, pain had decreased almost 80% from baseline in the treated group. [57]

Daily sitz baths and perianal massage may help with the discomfort associated with chronic prostatitis.

Frequent prostate massage was used extensively several decades ago and its use is still advocated by some in the treatment of difficult cases with persistent positive cultures despite appropriate antibiotic therapy.

 

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Consultations

Consultation with a urologist may be appropriate for men with relapsing chronic bacterial prostatitis (CBP) or for situations in which the diagnosis is unclear. A urologist may be able to properly perform the bacterial localization studies necessary to diagnose CBP (see Workup/Urinary Tract Localization Tests).

In the author's experience, most primary care physicians are not comfortable or experienced with obtaining the necessary specimens. Semen cultures or the 2-cup test with urine cultures collected before and following prostatic massage are simpler and represent effective alternatives to the 4-cup test.

Involvement of a multidisciplinary team approach has been recommended by the Prostatitis Expert Reference Group for patients who do not respond to initial treatments. The team may include urologists, pain specialists, nurse specialists, physiotherapists, cognitive behavioral therapists or psychologists, sexual health specialists, and general practitioners. [26]  Especially in patients with persistent pain, referral to pain specialists to target neuropathic pain should be considered. 

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Surgical Care

Surgery is usually not indicated for chronic prostatitis. However, in select situations when a patient has recurrent episodes of chronic prostatitis and improves with antibiotics, transurethral resection of the prostate (TURP) or transurethral vaporization of the prostate (TUVP) may remove a nidus of infection. This nidus may be in the form of prostatic stones, which are difficult to treat with antibiotic therapy alone. These stones are usually visible on transrectal ultrasonograms.

TURP/TUVP is performed in a standard fashion after preoperative antibiotics have been administered. Routine preoperative evaluation should be performed when planning for TURP/TUVP, and routine postoperative care for TURP/TUVP should be administered in these patients.

Prostatectomy

Prostatectomy is rarely indicated in the treatment of chronic bacterial prostatitis (CBP). When used, radical transurethral prostatectomy is suggested. This procedure may be more effective in men with prostatic calculi. Because most of the inflammation is located in the peripheral zone of the gland, an extensive resection of the gland is required to remove all infected and potentially infected tissue down to the level of the true prostatic capsule.

Only a single series of 10 patients, most with prostatic calculi, has been reported, but all 10 were considered cured. [58]  These authors concluded that the procedure is indicated, although only rarely, in men with well-documented bacterial infections in whom medical pharmacotherapy fails for 1 year.

For refractory cases, other authorities have suggested that transurethral microwave therapy to ablate prostate tissue has shown some benefit. [59]  At this time, this intervention should be considered only in patients in whom less-invasive therapies have failed but who do not desire radical transurethral prostatectomy. Larger series would be helpful to define the benefit of this procedure.

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Diet and Activity

Diet does not have an important role in treating CBP. Some physicians have advocated the avoidance of spicy foods, caffeine-containing products, tobacco and alcohol; however, no evidence has indicated any CBP-associated benefit from this. 

Activity changes do not have a prominent role in the treatment of CBP. However, the authors often advise patients to avoid bicycling or other activities that may put pressure on the perineal region. [37]

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Long-Term Monitoring

Patients should be followed up 4-6 weeks after initial presentation and further management should be guided by their symptoms.

If the patient is treated long-term with antibiotics, ensure that repeat localization studies of the prostate (ie, pre– and post–prostatic massage urine cultures after treatment) are conducted to conclude that the bacteria have been eliminated. If repeat cultures return positive results, prescribe a second course of antibiotics with a drug that has a different mechanism of action.

If repetitive courses of antibiotics fail but the patient has improved symptoms while on antibiotics, consider long-term, low-dose, suppressive therapy. Alternatives for suppressive therapy include single-strength TMP/SMX (one tablet qhs), trimethoprim (100 mg qhs), ciprofloxacin (250 mg qhs), and ofloxacin (200 mg qhs).

As with CPPS, symptom scores should be used to monitor improvements with different interventions. The following are the most commonly used tools:

  • National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI)
  • International Prostate Symptoms Score (IPPS)
  • Urinary, Psychosocial, Organ-specific, Infection, Neurological/systemic, Tenderness (UPOINT) classification
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