Detection of sexually transmitted pathogens in patients with chronic prostatitis/chronic pelvic pain: a prospective clinical study

Abstract

In <10% of patients with prostatitis syndrome, a causative uropathogenic organism can be detected. It has been shown that certain organisms that cause sexually transmitted infections can also cause chronic bacterial prostatitis, which can be hard to diagnose and treat appropriately because prostatic samples obtained by prostatic massage are not routinely tested to detect them. We conducted a clinical study to determine the prevalence of Chlamydia, mycoplasma, and trichomonas infection in 254 patients that were previously diagnosed and treated for chronic prostatitis/chronic pelvic pain syndrome due to negative urethral swab, urine, and prostate samples. Urethral swabs and standard Meares–Stamey four-glass tests were done. Detailed microbiological analysis was conducted to detect the above organisms. Thirty-five (13.8%) patients had positive expressed prostatic secretions/VB3 samples, of which 22 (10.1%) were sexually transmitted organisms that were not detected on previous tests.

Keywords

Diagnosis Europe men prostatitis sexually transmitted infections

Introduction

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) accounts for prostatitis-like symptoms in >90% of men. In <10% of patients with prostatitis syndrome, a causative uropathogenic organism can be detected.¹ The diagnosis of CP/CPPS is made by exclusion, and since the process is time consuming, it is often not done in clinical practice. Instead, patients are offered empirical therapy consisting of analgesics, antibiotics, and alpha blockers. The most common bacteria that cause chronic bacterial prostatitis are Gram-negative pathogens (Escherichia coli in 80% of cases) and enterococci that can be treated with fluoroquinolones. Those agents are usually detected by standard prostatic samples analysis. In contrast, Chlamydia trachomatis, mycoplasma/ureaplasma species, and Trichomonas vaginalis, that are common causes of sexually transmitted infections (STIs), can also cause chronic prostatitis, and prostate samples are not usually tested to detect them, even in clinical trials that evaluate CP/CPPS treatment.² Their significance has been confirmed in several clinical trials in which significant reduction of National Institute of Health Chronic Prostatitis Symptom Index (NIH-CPSI) scores after targeted therapy was shown.^3–7 Therefore, we conducted a prospective clinical study to find out the prevalence of uncommon pathogens in patients initially diagnosed and treated for CP/CPPS.

Methods

This was a prospective observational study performed in the University Hospital for Infectious Diseases ‘Dr. Fran Mihaljevic’, Zagreb, Croatia 2012 to 2015. We enrolled 254 consecutive patients who had been diagnosed with CP/CPPS in other institutions. The diagnosis was based on medical history, NIH-CPSI, clinical examination, and two- or four-glass test⁸ according to current guidelines, with exclusion of other causes of pelvic pain.¹ All patients had pelvic pain for at least three months and complained of lower urinary tract symptoms. All patients were pretreated according to CP/CPPS treatment regimens, but not within two weeks prior to inclusion. Patients were either referred or came for a consultation. The institutional ethics committee approved the study. Urethral swabs and standard Meares–Stamey four-glass tests were done. Patients gave standard first-void VB1 and midstream VB2 samples. After 2 min of prostatic massage the expressed prostatic secretions (EPS) were collected. Finally, all patients gave a postmassage urine sample (VB3). If EPS could not be obtained only VB3 was analyzed. We excluded patients who were not diagnosed according to current guidelines, who were taking antibiotics, or had positive urethral swab, VB1 and VB2 cultures. Quantitative segmented cultures and bacterial identification, as well as the number of leukocytes were determined in voided urine samples and EPS in the microbiology laboratory. Samples were cultured on solid media. Microbial growth was evaluated after 24 and 48 h. Pathogens were identified with biochemical/serological techniques. C. trachomatis was detected by PCR (Abbott real-time PCR, Abbott Molecular Diagnostics, USA); Mycoplasma genitalium and Ureaplasma urealyticum by semiquantitative cultures and antimicrobial susceptibility test Mycoplasma duo and S.I.R. (Mycoplasma tests, Bio Rad Laboratories) and T. vaginalis by additional culturing on modified diamond medium. All patients were treated with antibiotics (doxycycline, azithromycin, metronidazole), according to the isolated agent. Statistical analysis was performed using MedCalc for Windows, version 16.0 (MedCalc Software, Belgium).

Results

Median patient age was 41.4 years (IQR 33–50, range 24–62). Median duration of symptoms was six months (IQR 5–8, range 3–18). Median NIH-CPSI score was 19 (IQR 7–22, range 13–41). Median leukocyte count in EPS/VB3 was 5 (IQR 3–8, range 0–35). Of 254 patients, 30 had positive urethral swab, VB1 or VB2 cultures. EPS or VB3 cultures were contaminated in seven patients. Of the remaining 217 patients, EPS were obtained in 85 (39.2%), and VB3 alone was analyzed in the remaining 132 (60.8%) patients. There were 35/217 (16.1%) positive cultures: 16 EPS+VB3 cultures, and 19 VB3 cultures in the group where EPS were not obtained. A total of 22/217 (10.1%) cultures were positive for STIs. There was no contamination of those EPS and VB3 cultures. All PCRs for C. trachomatis were negative. There was no correlation between NIH-CPSI score, EPS/VB3 leukocyte count, and positivity of EPS/VB3 culture (Kendall rank correlation, Spearman rank correlation). Microbiological findings are shown in Table 1.

Table 1.

Isolated organism in two groups of patients.

Isolated organism	EPS obtained (N = 85)	EPS not obtained (N = 132)	Total (N = 217)
STI	12	10	22 (10.1%)
Mycoplasma genitalium	5	4
Ureaplasma urealyticum	2	3
Trichomonas vaginalis	5	3
Other	4	9	13 (5.9%)
Coagulase negative staphylococci	1	3
Enterococcus faecalis	1	2
Proteus spp.	1	1
Beta-hemolytic streptococci	1	1
Mixed flora	0	2

EPS: expressed prostatic secretions..

Discussion

In our study, we aimed to determine the prevalence of chronic bacterial prostatitis in patients initially diagnosed with chronic pelvic pain.

We found that 35/217 (16.1%) of patients who were initially diagnosed as CP/CPPS due to negative prostatic samples cultures had positive cultures. This can be explained by the significant rate of STI organisms that cannot be cultured by standard microbiological methods used for prostatic samples analysis. Such organisms are commonly isolated from urethral swabs but, despite initially negative swabs, organisms may still be present in the prostatic fluids, and in many cases prostate sample cultures are not tested for common STI agents. This is mostly due to the fact that they are difficult to culture and interpret and nucleic acid amplification testing is often unavailable. It may seem as a limit of this study that all patients were pretreated with various medications (nonsteroidal anti-inflammatory drugs, antibiotics, alpha blockers). This could have reduced the number of positive samples, and the washout period of two weeks may not have been long enough. Nevertheless, the overall number of positive samples with sexually transmitted organisms was likely not significantly influenced. The second limit of the study is the possibility that some of the participants initially had negative urinary tract samples, were correctly diagnosed with CP/CPPS, and later acquired the infection that we detected. This was reduced by detailed history and exclusion of patients with positive swab, VB1 and VB2 cultures.

In this study, we found a significant number of positive prostatic sample cultures among patients diagnosed with CP/CPPS. Since CP/CPPS is relatively uncommon in young patients, their prostatic samples should be tested for STI agents to exclude possible prostatic infection. Further cohort studies are needed to confirm the pathogenicity of these microorganisms.

Footnotes

Declaration of conflicting interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study is part of the project ‘Research on etiology, epidemiology, diagnostics and therapy of prostatitis syndrome’, funded by the Croatian Sciences Foundation.

References

Magistro

Wagenlehner

Grabe

. Contemporary management of chronic prostatitis/chronic pelvic pain syndrome. Eur Urol 2016; 69: 286–297.

Papeš D and Jerončić A. Determining the effect of alpha-blockers in chronic prostatitis/chronic pelvic pain syndrome: systematic review and meta-analysis. Eur Urol 2016; 70: e163–e165.

Skerk

Schönwald

Krhen

. Aetiology of chronic prostatitis. Acta Dermatovenerol Croat 2007; 15: 135–140.

Skerk

Krhen

Schonwald

. The role of unusual pathogens in prostatitis syndrome. Int J Antimicrob Agents 2004; 24: S53–56.

Magri

Marras

Skerk

. Eradication of Chlamydia trachomatis parallels symptom regression in chronic bacterial prostatitis patients treated with a fluoroquinolone-macrolide combination. Andrologia 2010; 42: 366–375.

Magri

Montanari

Škerk

. Fluoroquinolone-macrolide combination therapy for chronic bacterial prostatitis: retrospective analysis of pathogen eradication rates, inflammatory findings and sexual dysfunction. Asian J Androl 2011; 13: 819–827.

Vickovic

Skerk

Granic

. Metronidazole 1.5 gram dose for 7 or 14 days in the treatment of patients with chronic prostatitis caused by Trichomonas vaginalis: a randomized study. J Chemother 2010; 22: 364–365.

Meares

Stamey

. Bacteriologic localization patterns in bacterial prostatitis and urethritis. Invest Urol 1968; 5: 492–518.