Prostatitis: what is the role of infection

https://doi.org/10.1016/S0924-8579(02)00086-9Get rights and content

Abstract

Although bacterial prostatitis is a common diagnosis, well documented infections of the prostate are uncommon. Culture studies of prostate tissue led our group to hypothesize that bacterial colonization/invasion of the prostate gland might occur more commonly than is appreciated by standard microbiological techniques. Specific polymerase chain reaction (PCR) assays were used for each of the pathogens previously implicated in chronic prostatitis as well as broad-spectrum PCR assays to identify tetracycline resistance genes and bacterial ribosomal-encoding genes (16S rDNAs), followed by cloning and sequencing of the PCR products. Only ten (8%) of the 135 patients with chronic prostatitis had positive specific PCR assays including: Mycoplasma genitalium in four men, Chlamydia trachomatis in three and Trichomonas vaginalis in two, as well as one man positive for both M. genitalium and C. trachomatis. In contrast to the specific probes, the broad-spectrum PCR assays had a substantial proportion of positives. We found evidence of tetracycline resistance in 25% of patients. 16S rDNA-encoding sequences in 77% of the subjects. The tetracycline resistance positives were a subset of the 16S rDNA positive patients. Patients with 16S rDNA-encoding sequences were significantly more likely to have expressed prostatic secretion leukocytes. Many patients with chronic prostatitis/chronic pelvic pain syndrome have a wide variety of bacterial DNA-encoding sequences despite extensive negative microbiological investigations. Understanding the precise role of infection in this syndrome may well lead to better methods to elucidate the microbiology of the prostate in health and disease.

Introduction

Bacterial prostatitis is a common diagnosis and a frequent indication for antimicrobial therapy. Estimates are that 9–11% of the adult male population has symptoms of prostatitis at any given time [1], [2]. Prostatitis is also a common indication for antimicrobial therapy, with estimates that anywhere from 2 [2] to 8 million [3] outpatient visits are made per year in the United States, with antimicrobial agents prescribed for most patients.

The problem is that well documented infections of the prostate are exceedingly uncommon. For example, in our clinic, only about 7% of patients with chronic prostatitis have chronic bacterial prostatitis [4]. Standard uropathogens, that is, those organisms that cause bacteriuria, are thus identified in very few cases. Patients with bacteriuria are exceedingly important because they may have acute or chronic bacterial prostatitis. For these patients there is a very clear role for antimicrobial therapy and reasonable protocols [5] that have been validated in clinical trials [6], [7], [8]. Unfortunately, there are very few data on the aetiology of the other clinical syndromes and therefore, treatment is largely empirical and unsuccessful for many patients [9].

Most patients with prostatitis have no history of bacteriuria and very little evidence for bacterial infection in their prostates. Such patients were classified based on the presence or absence of leukocytes, in the traditional classification, as non-bacterial prostatitis for patients with leukocytes in their prostatic fluid, or as prostatodynia for patients without leukocytes in their prostatic fluid [10]. In the new consensus classification, patients are classified as having chronic prostatitis/chronic pelvic pain syndrome [11]. There are two subgroups. Patients with white cells in their prostatic fluid, post-massage urine, or seminal fluid are classified in the inflammatory category, while patients with white cells in none of these specimens are classified in the non-inflammatory category. There are very few data supporting rational treatment decisions for patients with either chronic inflammatory or chronic non-inflammatory chronic prostatitis/chronic pelvic pain syndrome.

There is some substantial empirical support for a potential role of genitourinary tract infections in chronic prostatitis/chronic pelvic pain syndrome [12]. Many patients relate the onset to sexual activity, often to an episode of urethritis. Antimicrobials often provide transient or partial relief of symptoms and standard practice is to provide multiple courses of antimicrobials [13], [14]. For example, in our study of 75 consecutive men evaluated for symptoms of chronic prostatitis, the average patient had received ten weeks of antimicrobial therapy in the 3 months before evaluation [4].

There are also microbiological data supporting a potential role of cryptic microorganisms in chronic prostatitis/chronic pelvic pain syndrome [12]. Organisms suggested as important in the literature include: Chlamydia trachomatis [15], [16], [17], [18], Ureaplasma urealyticum, other genital mycoplasmas [19], [20], [21], and the protozoan pathogen, Trichomonas vaginalis [22], [23]. Other organisms suggested as important in the literature are Neisseria gonorrhoea, which was a common cause of prostatitis in the pre-antibiotic era, genital viruses, particularly herpes simplex type 1, herpes simplex type 2, cytomegalovirus, fungi, and various other anaerobic and Gram positive bacteria [12], [14].

This article outlines our recent experience using a variety of microbiological and molecular biological methods to investigate the potential role of genitourinary tract infection in the difficult group of patients with chronic prostatitis/chronic pelvic pain syndrome.

Section snippets

Methods

In our initial studies we had very limited success in identifying pathogens in non-invasive genital tract specimens such as urine, expressed prostatic secretions and urethral swabs [4], [24]. This experience led us to investigate prostate tissue, obtained via the perineal approach and cultured in an anaerobic research lab [25]. In this study, we evaluated 85 men who met the current definition of chronic prostatitis/chronic pelvic pain syndrome. These patients had urethral swabs, lower tract

Results

This 5-year study evaluated 135 men by standard clinical evaluation, including history and physical, symptom scores, uroflowimetry, and an ultrasound residual urine determination. Microbiological studies included: studies for fastidious organisms (gonorrhoea, C. trachomatis, T. vaginalis, and genital mycoplasmas), lower urinary tract localization cultures, as well as chamber counts of expressed prostatic secretion leukocytes. These studies included a protocol with more than one thousand

Discussion

Our findings suggest that many patients with chronic prostatitis/chronic pelvic pain syndrome have a wide variety of bacterial DNA-encoding sequences despite extensive negative microbiological investigations. Our findings also suggest that some patients with chronic prostatitis/chronic pelvic pain syndrome may have C. trachomatis, T. vaginalis and M. genitalium in their prostates despite having no evidence of urethritis and negative urethral cultures or antigen tests for these pathogens.

References (35)

  • M.C. Roberts et al.

    Detection of Tet M and Tet O tetracycline resistance genes by polymerase chain reaction

    Mol. Cell. Probes

    (1993)
  • M.C. Roberts

    Epidemiology of tetracycline-resistance determinants

    Trends Microbiol.

    (1994)
  • S. Keay et al.

    Polymerase chain reaction amplification of bacterial 16s rRNA genes in prostate biopsies from men without chronic prostatitis

    Urology

    (1999)
  • W.W. Hochreiter et al.

    Evaluation of the bacterial flora of the prostate using a 16S rRNA gene based polymerase chain reaction

    J. Urol.

    (2000)
  • J.N. Krieger et al.

    Bacterial DNA sequences in prostate tissue from patients with prostate cancer and chronic prostatitis

    J. Urol.

    (2000)
  • Gushchin BL, Francis ME. Epidemiological data on the prevalent diagnostic and treatment procedures for chronic...
  • T. Stamey

    Urinary infections in males

  • Cited by (50)

    • Specific expression pattern of tissue cytokines analyzed through the Surface Acoustic Wave technique is associated with age-related spontaneous benign prostatic hyperplasia in rats

      2018, Biochemistry and Biophysics Reports
      Citation Excerpt :

      The etiology of prostatic inflammation is not completely elucidated. At this time, the current data seems to indicate that the onset of prostatic inflammation is launched under a multifactorial etiological basis that involves factors such as infection [12,13], systemic inflammation, components from both the environment and the diet, oxidative stress, urine reflux and systemic steroids [14]. Despite this, according to the literature, only ageing and androgenic imbalance, either concomitantly or not, has been definitely related to BPH development [15–17].

    • Prostate inflammation: A brief review

      2017, Urological Science
      Citation Excerpt :

      One study showed that only 8% patients with chronic prostatitis had positive specific PCR assays. Many patients with chronic prostatitis have a wide variety of bacterial DNA-encoding sequences despite extensive negative microbiological investigations.36 Acute and chronic inflammatory infiltrates can both be found in the prostate.44

    • High fat diet promotes prostatic basal-to-luminal differentiation and accelerates initiation of prostate epithelial hyperplasia originated from basal cells

      2016, Stem Cell Research
      Citation Excerpt :

      This basal-to-luminal differentiation is essential for initiation of prostate cancer with a basal cell origin (Kwon et al., 2014). However, acute bacterial infection in the prostate is relatively rare in human patients (Krieger & Riley, 2002). Therefore, the relevance of the bacterial infection-induced basal-to-luminal differentiation to the human prostate-related diseases is uncertain.

    • Oxidative stress in prostate cancer

      2009, Cancer Letters
      Citation Excerpt :

      This belief is strengthened by the isolation of gram negative enteric bacteria commonly associated with urinary tract infections from the affected prostate [92]. However, a wide spectrum of organisms have also been identified to be involved in prostatitis; from Enterobacteria like Escherichia coli, Enterococcus fecalis, and Proteus mirabilis to Chlamydia spp. and Ureaplasma spp. [94]. This has strengthened the belief of possible contiguous spread from other sources including the bladder, bowels, blood or the lymph to prostate [95].

    View all citing articles on Scopus
    View full text