United Kingdom National guideline for the management of prostatitis (2008)

Clinical Effectiveness Group

British Association of Sexual Health and HIV

Introduction and Methodology

Scope and Purpose: This guideline offers recommendations on the management of acute and chronic prostatitis in the setting of genitourinary medicine clinics. It applies primarily to men aged 18 years or older presenting to health care professionals, working in departments offering level 3 care in Sexual Health (see national strategy) within the United Kingdom. However, the recommendations should prove useful in other settings such as urology and primary care.

Stakeholder involvement: The authors are clinicians working in this field. Members of BASHH have had the opportunity to comment on the guideline, prior to publication.

Rigour of Development: Search Strategy – Medline Search 1996-2006 using keyword “prostatitis” “pelvic pain, male” and “chronic pelvic pain, male”. Cochrane Database of Systematic reviews and the Cochrane Controlled Trials Register up 2007 using keyword “prostatitis”. Additional studies and review articles were identified through a manual search of bibliographies of retrieved articles

Inclusion/exclusion of evidence criteria: Where available systematic reviews were used. Studies were limited to humans and English language.

The previous guidelines (published in 2000) were used as a framework that was revised and updated.

Classification

Prostatitis is classified into the following categories as recommended by the US National Institutes for Health (NIH) [1]

I Acute bacterial prostatitis

II Chronic bacterial prostatitis

III Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS)

A Inflammatory

B Non-inflammatory

(This division, based on the four-glass test, has not been shown to be of any clinical or prognostic significance ([2])

IV Asymptomatic inflammatory prostatitis

(This is a histological diagnosis in patients undergoing a prostate biopsy and is not discussed further in these guidelines.)

Acute and chronic bacterial prostatitis account for <5% of all prostatitis diagnoses; their precise incidence is unknown.

Acute Prostatitis

Aetiology

Acute prostatitis is caused by urinary tract pathogens [3]. These include:

  • Gram negative organisms, most commonly Escherichia coli, Proteus spp, Klebsiella spp and Pseudomonas spp
  • Enterococci
  • Staphylococcus aureus due to prolonged catheterisation
  • Rarely anaerobes such as Bacteroides spp

Mode of Transmission

Infection may spread from the distal urethra/urethral meatus but can also spread from the bladder, blood and lymphatic system. Acute prostatitis is an uncommon complication of UTI.

Clinical features

Symptoms [4,5,6]

Acute prostatitis is an acute severe systemic illness.

Symptoms include:

  • symptoms of a urinary tract infection: dysuria, frequency and urgency
  • symptoms of prostatitis: low back pain, perineal, penile and sometimes rectal pain
  • symptoms of bacteraemia: fever and rigors; arthralgia and myalgia may occur

Signs [4,5,6]

Signs include:

  • signs localised to the prostate: an extremely tender, swollen and tense, smooth textured prostate gland which is warm to the touch
  • signs of the bacteraemia: pyrexia and tachycardia

Complications

Patients with acute prostatitis may present with acute retention secondary to prostatic oedema

Prostatic abscess, bacteraemia, epididymitis and pyelonephritis.

Diagnosis

Mid-stream urine sample for dipstick testing, culture for bacteria and antibiotic sensitivity

Blood cultures for bacteria and antibiotic sensitivity

  • Prostatic massage should not be performed on patients with acute bacterial prostatitis. This may be painful, can precipitate bacteraemia, and is likely to be of little benefit as pathogens are almost always isolated from urine.
  • Management

General Advice

Adequate hydration should be maintained, rest encouraged and analgesics such as non-steroidal anti-inflammatory drugs if required

Treatment

  • As acute prostatitis is a serious and severe illness empirical therapy should be started immediately after blood and urine cultures have been obtained.
  • Parenteral or oral treatment should be selected according to the clinical condition of the patient. If there is deterioration or failure to respond to oral therapy urgent admission and parenteral therapy should be arranged.
  • Good antibiotic penetration into all areas of the prostate gland is achieved because of the intense inflammation.
  • Antibiotics should be continued or changed according to sensitivity results.
  • If acute retention occurs suprapubic catheterisation should be performed to avoid damage to the swollen prostate [6].

Recommended Regimens

For patients requiring parenteral therapy antibiotics covering the likely organisms should be used [7].

  • A high dose broad spectrum cephalosporin (for example, cefuroxime, cefotaxime or Ceftriaxone) plus gentamicin (level of evidence IV, grade of recommendation C)
  • When clinically improved the therapy can be switched to oral treatment according to sensitivities.

For patients suitable for oral therapy, quinolones can be used [8,9]:

  • Ciprofloxacin 500mg twice daily for 28 days (IV, C) [9]

or

  • Ofloxacin 200mg twice daily for 28 days (IV, C) [10,11].

Allergy

For patients intolerant of, or allergic to, quinolones an alternative is:

  • Trimethoprim 200mg twice daily for 28 days (IV, C).

Sexual partners

Treatment of sexual partners is not required.

Follow-up

  • If the patient fails to respond fully to therapy the diagnosis of a prostatic abscess should be considered [12]. This can be confirmed by transrectal ultrasound scan or computed tomography scan of the prostate. If present, perineal or transurethral drainage is necessary [6].
  • If acute prostatitis is managed correctly the prognosis is good. The optimal duration of treatment is not known. 4 weeks of antibiotic therapy is usually recommended to reduce the risk of developing chronic bacterial prostatitis [4].
  • Following recovery, the urinary tract should be investigated to exclude a structural cause for urinary tract infection.
Chronic Bacterial Prostatitis (CBP)

This is chronic bacterial infection of the prostate with or without symptoms of prostatitis, and with a history of recurrent urinary tract infections caused by the same bacterial strain without any structural abnormalities. It is rare in comparison to CP/CPPS.

Aetiology

The usual causative bacteria are those causing urinary tract infection, most commonly E coli [13]. Some Gram positive organisms such as Staphylococcus aureus and Enterococcus faecalis may cause CBP [14,15]. The role of other Gram positive organisms such as coagulase negative staphylococci, non-group D streptococciand diptheroids remains controversial and subject to debate [16].

Clinical Features

Symptoms

Typically there is a history of recurrent or relapsing urinary tract infection, urethritis or epididymitis.

Patients frequently report genitourinary and pelvic pain / discomfort during a flare-up and alleviation of symptoms after antibiotic treatment.

They may be asymptomatic between acute episodes or have mild pelvic pain or irritative voiding symptoms (frequency, urgency).

Signs

Apyrexial, no systemic signs.

The patient may have a diffusely tender prostate during acute episodes otherwise no objective clinical signs.

Diagnosis

This is usually based on history of recurrent urinary tract infections by the same bacterial strainand the exclusion of other causes. In particular, no structural reason for recurrent urinary tract infection is identified on urinary tract imaging.

Investigations

1. Urine dipstick test (for evidence of urinary tract infection or other abnormality that may require investigation e.g. haematuria).

2. MSU - urine cultures are sterile unless an acute urinary tract infection is present - review past MSU results.

3. Urinary tract imaging (ultrasound or IVU) to exclude structural abnormalities.

4. Lower urinary tract localisation study or “four-glass test” (see appendix 1 for details of this). The reliability of this test is not known because a gold standard for the diagnosis is not available. The four-glass test is not widely used in clinical practice and may not alter patient management [17]. Nonetheless, in suspected CBP it may be considered and can confirm the diagnosis.

5. Urodynamics – may be considered, to exclude other conditions predisposing to recurrent UTI.

Management

General advice

Patients should be given a detailed explanation of their condition – that the prostate is a focus of infection which causes recurrent urinary tract infection with particular emphasis on the long-term implications for their health and the possibility of further episodes of urinary tract infection unless the focus is eradicated by successful treatment. Clear and accurate written information can help to reinforce this.

Treatment

Antibiotic treatment should be chosen according to bacterial cultures and sensitivities.

Fluoroquinolones have become standard of care in CBP (Ib, A) – they have good penetration of the prostate gland and broad spectrum activity against both gram-negative and gram-positive organisms [18,19,20]. Most comparative studies have shown similar rates of clinical success and/or bacteriological cure for the fluoroquinolones [20]. The recommendations for other antibiotics are based on small studies plus expert opinion.

Recommended regimens

For patients with CBP first-line treatment is with a quinolone such as [20]

  • Ciprofloxacin 500mg twice daily for 28 days (Ib, A) [15,21]

or

Levofloxacin 500mg od for 28 days (Ib,A) [15,22]

or

Ofloxacin 200mg twice daily for 28 days (III, B) [23.24]

or

  • Norfloxacin 400mg twice daily for 28 days (III, B) [25,26]

Side effects of quinolones – generally well tolerated but tendon damage including rupture has occurred very rarely. Recent FDA recommendations include advising the patient that at the first sign of tendon pain, swelling or inflammation they should stop taking the drug, avoid exercise and use of affected area and contact their doctor [27].

Allergy

For those allergic to quinolones or in patients recommended to avoid quinolones (epilepsy or prone to seizures) treatment should be selected according to antibiotic sensitivities of the bacterial isolate, and an antibiotic with good penetration into the prostate should be chosen.

There is poor evidence for these alternative antibiotics.

Options include:

  • Minocycline 100mg twice daily for 28 days [28] (III, B) (In practice most experts would use doxycycline 100mg twice daily for 28 days because of more toxicity with minocycline.)

or

  • Trimethoprim 200mg twice daily for 28 days (IV,B)

If minocycline or doxycycline are used antibiotic sensitivity testing is important, as many urinary pathogens are tetracycline resistant.

Alpha blockers – there is small amount of evidence that adding in alpha blockers to antibiotics may improve symptoms of chronic bacterial prostatitis and relapse rate but the study was difficult to analyse [29]. Some investigators have reported the use of submucosal injections of antibiotics but this approach is not widely used [30].

Follow-up

Patients with CBP are at risk of relapse and should have a repeat MSU after completing treatment.

For recurrent UTI after 28 days of treatment, further investigation for predisposing conditions should be considered, antibiotic sensitivities should be rechecked and the treatment repeated. Prolonged courses of antibiotic (e.g. 3 months) may be tried but have not been studied systematically.

Prostatic calculi have been suggested as a source for recurrent infection [6]. They are very common radiographically [31,32]. Radical transurethral prostatectomy or total prostatectomy have been reported to be effective in a small number of patients if they are selected carefully and for very specific indications, but usually this is not justified [33,34].

Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS)

Introduction

This is a common chronic condition with estimates of between 2 and 14% lifetime prevalence [35,36,37,38].

It cannot be rigidly defined but a suggested definition is the presence of typical symptoms of discomfort or pain in the genital or pelvic region for more than 3 months within the past 6 months [39].

Aetiology

Unknown aetiology, may be multifactorial.

Proposed mechanisms include:

  • Infection (there is no evidence that CPPS is caused by an STI) [13,40,41]
  • Immunological [42,43,44,45,46]
  • Autoimmunity [47,48]
  • Neuromuscular spasm/pelvic floor muscle dysfunction [49,50]
  • Intraprostatic urine reflux [51,52,53,54]
  • Voiding dysfunction leading to increased intraprostatic pressure [54]
  • Neurogenic inflammation [55]
  • Functional somatic syndrome [56,57]
  • Chronic pain syndrome [58,59]

Clinical features

Symptoms

Urological pain [1] including

  • perineal pain
  • lower abdominal pain
  • penile pain (especially penile tip)
  • testicular pain
  • rectal and lower back pain
  • ejaculatory pain

Patients also complain of variable irritative and obstructive symptoms and/or ejaculatory disturbance [60].

The constellation of symptoms appear to be relatively similar and consistent in men with CP/CPPS [61].

The symptoms usually remain constant although some men have large fluctuations in the severity of symptoms over time [61].

Strictly, symptoms should have been present for at least 3 months to diagnose CPPS [1] although in practice the diagnosis is often suspected after a shorter duration of symptoms (see definition above).

There are several exclusion criteria for the diagnosis –

  • Active urethritis, urogenital cancer, urinary tract disease, functionally significant urethral stricture or neurological disease affecting the bladder[1]

Assessment of symptoms

Symptom inventory or index (NIH CPSI) (see appendix 2)

This is a validated symptom questionnaire that scores on pain, voiding dysfunction and quality of life [62]. It should not be used to diagnose CP/CPPS but may be useful as an evaluative tool to assess current symptoms and their impact. It is also useful in assessing changes in symptom severity and impact during follow up, and as an outcome measure following treatment [63].

Signs

There are few objective clinical signs and the prostate gland may, or may not, be locally or diffusely tender to palpation.

Complications

Significant physical and psychological impact – cross-sectional studies have shown sickness impact scores comparable to those with angina and Crohn’s disease [64] and mental health scores worse than the most severe subgroups of diabetes mellitus and chronic heart failure [65].

Diagnosis

There is no gold standard diagnostic test for this condition, therefore CP/CPPS is a diagnosis of exclusion [66].

Diagnosis is usually made on a typical history and not on examination or investigation findings.

The initial diagnostic evaluation of a patient presenting with pelvic pain should consider the possibility of other underlying disease or disorder that could cause the symptoms [67]. Atypical presentations may require investigation to exclude other conditions before the diagnosis is made.

Initial screening should involve taking a complete history, examination including digital rectal examination, urinalysis and MSU microscopy and culture [66,67,68].

Test no longer recommended:

Lower urinary tract localisation study (four-glass test) (see appendix 1 for details of this)

Recent studies have reported that localising leucocytes/bacteria to the prostate cannot accurately differentiate between men with CP/CPPS and men without symptoms [2] and results of the test do not correlate with duration, frequency and severity of symptoms [69]. The test procedure has not been standardised [70]. Some argue that the test should be confined to research. It is not widely used in clinical practice [17,71] and may not alter patient management [72]. Therefore the test cannot be recommended in the routine investigation of CP/CPPS.

Further tests that may be considered:

STI screen

Non-specific urethritis (NSU), chlamydia and gonorrhoea should be excluded.

In selected patients:

Urine cytology – if the patient has microscopic haematuria with frequency, urgency and dysuria urine cytology should be performed to help exclude lower urinary tract malignancy [73]. Patients with unexplained haematuria should be referred to an urologist.

PSA – PSA is recommended if indicated by abnormal prostate on digital rectal examination [74]. Prostatic tenderness is not an indication. PSA can be elevated during active inflammation of the prostate [75].

Simple urodynamics [76] – may identify bladder neck dysfunction, bladder outflow obstruction and incomplete bladder emptying particularly in those with urinary symptoms.

Transrectal ultrasound (TRUS) – is not useful in differentiating the various forms of chronic prostatitis [77]. TRUS may identify prostatic calcification but the significance of this is uncertain. Anecdotal reports indicate that TRUS may rarely identify a treatable prostatic abscess or cyst, seminal vesicle or ejaculatory duct abnormality [78](which may present with ejaculatory pain), but its routine use in the investigation of suspected CP/CPPS is not justified.

Patients with atypical presentations of CP/CPPS and unexplained urological symptoms should be referred to a urologist.

Management

General advice

Patients should be given a detailed explanation of their condition with reassurance, indicating that CP/CPPS is a non-malignant condition and not a sexually transmitted infection that has a tendency to persist [79]. The cause has not been determined with certainty but infection is unlikely. Diagrams and written information (a leaflet) may be helpful. (further information can be obtained from

Treatment

There are no reliably effective treatments for CP/CPPS [66,80,81]. Few randomised, controlled trials are available and no large scale, well-designed trials have been conducted. An observational report from a specialised prostatitis clinic reported reasonable clinical results in only one third of patients with monotherapy [82]. This may not reflect the prognosis in newly diagnosed patients. Multimodal therapy (i.e. using multiple treatment types simultaneously) has therefore been proposed but this is not based on evidence from randomised trials [83].

Treatment should be individualised as CP/CPPS is not a standardised disease or specific inflammatory process but rather a clinical syndrome.

Antibiotics (III,C)

There is no convincing evidence that antibiotics are effective in CP/CPPS. Many clinicians try antibiotics initially, as there is evidence that some patients benefit in uncontrolled clinical studies [84].

The effects of antibiotics could be a placebo effect as there appears to be a large placebo effect in most RCTs in this condition[85,86,87] or related to anti-inflammatory properties of some antibiotics such as doxycycline and fluoroquinolones [88,89];or antibiotics may eradicate bacteria that are not routinely cultured or culturable.

Two recent RCTs have shown no benefit of antibiotics versus placebo but both of these studies were in heavily pretreated patients [83,85]. The value of antibiotic treatment in treatment naive men has not been assessed.

The toxicity of antibiotics, particularly prolonged use of fluoroquinolones, must also be considered. There is also concern that use of fluoroquinolones may increase susceptibility to C. difficile infection [90].

Alpha-blockers (Ia,A)

There is modest evidence of their efficacy in CP/CPPS and a trial should be considered in patients with troublesome persistent symptoms. A systematic review showed a relative risk of improvement of 0.57 translating as number needed to treat of 6 [80]. The evidence suggests prolonged treatment is needed (14-24 weeks) to show a clinically significant effect and benefits appear greatest in those naïve to alpha-blockers.