Surgical management of National Institutes of Health category II chronic bacterial prostatitis: a case series and scoping review of the literature

Introduction

Background

Prostatitis is a generic term referring to several distinct syndromes with different etiologies. The National Institutes of Health (NIH) classification scheme describes four categories of prostatitis including: acute bacterial prostatitis (ABP) (category I), chronic bacterial prostatitis (CBP) (category II), chronic prostatitis/chronic pelvic pain syndrome (category III) and asymptomatic inflammatory prostatitis (AIP) (category IV) (1). Category II presents as recurrent urinary tract infections (UTIs), caused by the same bacterial strain which can be recovered from the prostate between symptomatic infections (2).

Rationale and knowledge gap

Some patients can be managed medically with antibiotic therapy and/or alpha blockade. However, there is a subset of patients with disease refractory to conservative management and thus may be eligible for surgical intervention. These patients must be carefully selected as there is no evidence to justify surgery is appropriate for categories III or IV (3). If the infection is due to incomplete bladder emptying from benign prostatic hyperplasia (BPH), then relief of obstruction is the goal. If the infection is due to a nidus within the prostate, often within prostatic calcifications, then the infected tissue must be completely removed. If all stones are within the surgical capsule, then a BPH procedure is acceptable but otherwise, the entire prostate would need removal. The literature has described transurethral resection of the prostate (TURP), laser therapy, holmium laser enucleation of the prostate, and robotic radical prostatectomy as viable treatment options (1-8). There has not been any case series describing the outcomes of men who have undergone surgical intervention for CBP.

Objective

The purpose of this case series is to present outcomes of patients who have undergone various surgical therapies to treat CBP. Secondarily, we provide a review of the current literature concerning surgical management of NIH category II prostatitis. We present this article in accordance with the PRISMA-ScR reporting checklist (available at https://tau.amegroups.com/article/view/10.21037/tau-23-142/rc).

Methods

Case series

This is a single-center retrospective case series of men seen at Cleveland Clinic Glickman Urological and Kidney Institute for the diagnosis of refractory NIH category II CBP and managed with surgical intervention. All surgeries were performed by a single surgeon. Diagnosis of CBP was established based on the presence of recurrent culture-proven UTI, prostatic secretion infections, and documentation of negative urine cultures in the asymptomatic period if possible. All patients came to our tertiary referral center with extensive histories of multiple antibiotic courses. Outside records were used to confirm this. Cure was defined as lack of recurrence of infection after surgical treatment. Only patients who underwent surgery were included; patients who received a diagnosis of chronic prostatitis incidentally after surgical treatment of BPH were excluded from this study. In the perioperative period, baseline cefazolin was used on induction. An additional antibiotic was included based on each patient’s prior culture history; this was typically an aminoglycoside or a quinolone. Antibiotics were continued orally for at least 2 weeks beyond the perioperative period for patient who were already on long-term low dose therapy. Relevant patient history, perioperative details, and outcomes were obtained from the electronic medical record. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study was approved by the institutional review board of the Cleveland Clinic (IRB No. 21-462). Informed consent was not required from patients included in this study as it was a retrospective study with participants from various states/countries. Prostatic stones were identified by transrectal ultrasound (TRUS) and/or computed tomography scan (CT scan). Although most patients arrived with outside CT scans, TRUS was always performed on-site to assess for presence of stones and whether stones were completely contained within the surgical capsule. Normally distributed values were reported as mean ± standard deviation and nonparametric values were reported as median (interquartile range).

Scoping review

PubMed was queried with the following searches: “chronic bacterial prostatitis” OR ((“category ii”[All Fields] OR “category 2”[All Fields]) AND prostatitis) OR “bacterial chronic prostatitis” OR “ii prostatitis” OR (chronic[ti] (bacteri*[ti] NOT non-bacteri*[ti]) prostatitis[ti]) AND “Prostatectomy”[Mesh] OR prostatectom* OR (“prostate gland” remov*) AND holmium laser OR HoLEP OR (Laser Therapy[MeSH] AND Holium[MeSH]) AND (transurethral resection*) OR TURP OR Transurethral Resection of Prostate[MeSH]. Additional articles were obtained by reviewing the references of relevant manuscripts. Date restrictions were not placed on the search. Exclusion criteria included: lack of relevancy to the present study, manuscripts in languages other than English, retracted and duplicate articles. The data were reviewed independently by two members of the research team, with a third member available for any discordant findings. The data were organized into a narrative summary for further discussion. Variables sought included: prostatitis classification, definitive diagnosis of CBP, outcomes, and complications, and time to follow-up.

Results

Endoscopic management

Twelve patients underwent endoscopic procedures intended to remove the source of infection. The mean age of patients in this subgroup was 71 years with a mean prostate volume of 50 cc. There were no acute infections in the post-operative period. Six of the 12 patients in this subgroup had prostatic stones. 2 of the 12 (16.7%) patients had CBP recurrence following surgery with E. Coli at 12 and 60 months; both patients initially had prostatic stones. One of these patients with CBP recurrence developed a urethral stricture following laser therapy. Individual patient follow-up outcomes, endoscopic procedure, and clinical characteristics are listed in Table 1.

Robotic total prostatectomy

Seven patients were treated with nerve-sparing robotic total prostatectomy for suspected source of infection outside of the surgical capsule. Median age of this subset was 67 years with a mean prostate volume of 31.2 cc. There were no acute infections in the post-operative period. Three of seven (43%) patients in this group had previously undergone TURP with life-threatening UTIs isolated to the prostate before robotic prostatectomy. Two patients in this subgroup had concomitant Gleason score six prostate cancer and one patient had Gleason score seven prostate cancer, diagnosed on prior prostate biopsy. Three patients had prostate stones, two of which had prostatic stones that extended beyond the surgical capsule. All subjects were diagnosed with CBP; two of the seven patients had a history of NIH category I prostatitis. E. coli was the isolated pathogen for six patients with two of these being MDR E. coli. Serratia and vancomycin resistant enterococcus (VRE) were each isolated in one subject, respectively.

Postoperatively, one patient (14.3%) experienced recurrent UTIs. While 6 of 7 patients in this subgroup were cured of CBP, one patient reported erectile dysfunction. One patient with Gleason six prostate cancer reported stress urinary incontinence at 72 months follow-up. Another patient with Gleason seven prostate cancer reported stress urinary incontinence at 84 weeks follow-up. Clinical characteristics of the patients, outcomes, and complications are detailed in Table 1.

Scoping review

After conducting a comprehensive scoping review of available articles, it became evident that the majority of existing literature regarding CBP focuses on medical management of the condition. The literature screening strategy is depicted in Figure 1. Despite studies stating patients were diagnosed with CBP, the literature consistently fails to mention definitive diagnosis of CBP with prostatic secretion cultures or even urine cultures prior to surgical intervention. For the few articles that study the outcome of curing patients definitively diagnosed with CBP, the results often combined these patients with patients of category III prostatitis rather than maintaining stratified results of patients in their cohort or focused on the primary outcome of symptom relief rather than curing of recurrent infection. As a result, no studies were found on the curative outcomes of surgical intervention on patients with CBP (3,9-28). One study by Cunha et al. did show TURP was unsuccessful in curing their patient with CBP due to remnant prostatic calcifications being left behind and serving as a nidus for continual infection. However, this study is primarily a testament to combination medication therapy as being more efficacious to treat CBP, and the focus was not on the efficacy of TURP on curing CBP (26). Thus, our study provides one of the first single-center retrospective case series of adult patients with refractory NIH category II CBP managed with surgical intervention.

Figure 1 Identification of studies for review.

Discussion

Key finding

Between all modalities rate of cure was 84%. The available literature does not include patients with definitive diagnosis of CBP with prostatic secretion culture or urine cultures prior to surgical intervention. Furthermore, studies that assessed surgical outcomes did not properly stratify NIH categories of prostatitis or capture infection cure rates; thus, there were no studies of curative outcomes in patients with NIH category II CBP. When disease is confined to the surgical capsule, endoscopic management is likely sufficient. In patients with disease beyond the capsule and/or concomitant prostate cancer, prior endoscopic treatment, or life-threatening UTI, radical prostatectomy may be justified. Of note, only symptoms related to outflow obstruction were improved immediately by surgery. None of the cases in this series resulted in acute infections in the post-operative period. Insurance coverage for endoscopic procedures and radical prostatectomy was easily obtained about surgeons in this study.

Comparison with similar research

Fewer than 10% of outpatient prostatitis visits are for true CBP, however, it can be a challenging disease to treat. This condition is defined by recurrent UTIs of the same causal organism interspersed with asymptomatic periods. Despite urinary tests suggesting bacterial clearance, prostatic secretions during the asymptomatic period will show persistence of the same bacteria—confirming the source of infection to be the prostate. These diagnostic criteria help to distinguish category II prostatitis from the more common, NIH category III prostatitis (29). First-line treatment for NIH category II prostatitis includes a 4-to-6-week course of antibiotics such as macrolides, sulfa drugs, tetracyclines and fosfomycin. Fosfomycin may be used to treat patients with multidrug resistant organisms or refractory disease. In addition to medication, prostatic massages with or without antibiotics may also alleviate symptoms (30,31). In cases of relapse, patients may be prescribed long-term low dose antibiotics, however, there are concerns for antibiotic resistance with this strategy (29). As a result, in selected patients, surgery is a viable treatment option for CBP and it provides an opportunity for patients to be cured. TURP and radical (total) prostatectomy are the primary surgical treatments for refractory CBP and are most beneficial in men with incomplete bladder emptying, significant prostatic stone burden and/or recurrent drug resistant infection (29).

Our case series is unique in that we demonstrate that endoscopic procedures typically used to treat BPH such as holmium laser enucleation of the prostate, photo-vaporization of the prostate, and TURP are effective therapies for patients with disease confined to the surgical capsule. However, these procedures are limited in their use if the nidus of infection is beyond the surgical capsule. As predicting or testing for the exact source of the infection is difficult given the current diagnostic tools, total prostatectomy offers a more robust treatment option. Total prostatectomy done in this setting without a concern for cancer should have a lower side effect profile than true radical prostatectomy given that nerves can be spared and no lymph node dissection is necessary however complications such as erectile dysfunction and urinary incontinence are still possible. In our study, patients who underwent nerve sparing total prostatectomy had prostate stones known to extend outside the surgical capsule, a history of prior TURP with life threatening UTI’s isolated to the prostate, or concomitant prostate cancer. Even after this robotically invasive surgery, there is still the possibility that the recurrent UTI was not caused by the prostatic focus as evidenced by our one patient with recurrent UTI following removal of the prostate.

Strengths and limitations

The strengths of our study include careful evaluation and diagnosis of infection localization and stone burden prior to surgery and a unified algorithmic approach within the same clinic. The study is limited by sample size and the inability to perform clean localization cultures on select patients due to inability to discontinue antibiotics.

Implications and actions needed

Studies with larger cohorts across a diversity of patient populations would support these findings from an academic tertiary care referral center.

Conclusions

In well-selected patients, endoscopic management or radical prostatectomy may be curative in CBP that does not resolve with antibiotics. The literature surrounding this topic is limited in its utility due to absence of proper patient stratification and definitive culture proven disease.

Acknowledgments

Funding: None.

Footnote

Reporting Checklist: The authors have completed the PRISMA-ScR reporting checklist. Available at https://tau.amegroups.com/article/view/10.21037/tau-23-142/rc

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-23-142/coif). DS serves as an unpaid editorial board member of Translational Andrology and Urology from August 2022 to July 2024. SDL reports that he received a grant from the American Urological Association. DS reports receiving payment for the American Urological Association Board Review course. He is paid for 5 lectures, all unrelated to the subject of this paper. He reports patents planned but unrelated to this work. He reports roles on several boards which are all medical non-profits and unpaid positions. Finally, he reports stock or stock options with Triural licenses nutraceuticals for category III prostatitis. He is also currently a full-time employee of Pacific Edge Diagnostics whose products in bladder cancer are completely unrelated to the subject of this paper. The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study was approved by the institutional review board of the Cleveland Clinic (IRB No. 21-462). Informed consent was not required from patients included in this study as it was a retrospective study with patients from various states/countries.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Krieger JN, Nyberg L Jr, Nickel JC. NIH consensus definition and classification of prostatitis. JAMA 1999;282:236-7. [Crossref] [PubMed]
2. Nickel JC. Prostatitis. Can Urol Assoc J 2011;5:306-15. [Crossref] [PubMed]
3. Barnes RW, Hadley HL, O'Donoghue EP. Transurethral resection of the prostate for chronic bacterial prostatitis. Prostate 1982;3:215-9. [Crossref] [PubMed]
4. Krongrad A, Lai S. Laparoscopic prostatectomy for severely symptomatic, treatment-refractory chronic prostatitis: Preliminary observations from an ongoing phase II clinical trial. Urotoday Int J 2011;4:art30. [Crossref]
5. Alexander RB. Radical prostatectomy for chronic prostatitis. BJU Int 2003;92:e17. [Crossref] [PubMed]
6. Wagenlehner FM, Diemer T, Naber KG, et al. Chronic bacterial prostatitis (NIH type II): diagnosis, therapy and influence on the fertility status. Andrologia 2008;40:100-4. [Crossref] [PubMed]
7. McLoughlin LC, McDermott TE, Thornhill JA. Radical prostatectomy in the presence of ongoing refractory ESBL Escherichia coli bacterial prostatitis. BMJ Case Rep 2014;2014:bcr2014206291. [Crossref] [PubMed]
8. Schoeb DS, Schlager D, Boeker M, et al. Surgical therapy of prostatitis: a systematic review. World J Urol 2017;35:1659-68. [Crossref] [PubMed]
9. Su ZT, Zenilman JM, Sfanos KS, et al. Management of Chronic Bacterial Prostatitis. Curr Urol Rep 2020;21:29. [Crossref] [PubMed]
10. Feng Y, Ramnarine VR, Bell R, et al. Metagenomic and metatranscriptomic analysis of human prostate microbiota from patients with prostate cancer. BMC Genomics 2019;20:146. [Crossref] [PubMed]
11. Smart CJ, Jenkins JD, Lloyd RS. The painful prostate. Br J Urol 1975;47:861-9. [Crossref] [PubMed]
12. Krieger JN. Prostatitis syndromes: pathophysiology, differential diagnosis, and treatment. Sex Transm Dis 1984;11:100-12. [Crossref] [PubMed]
13. Krieger JN, Riley DE, Vesella RL, et al. Bacterial dna sequences in prostate tissue from patients with prostate cancer and chronic prostatitis. J Urol 2000;164:1221-8. [Crossref] [PubMed]
14. Baert L, Van Poppel H, Vandeursen H. Review of modern trends in the treatment of chronic bacterial prostatitis (C.B.P.). Infection 1991;19:S157-9. [Crossref] [PubMed]
15. Srigley JR. Key issues in handling and reporting radical prostatectomy specimens. Arch Pathol Lab Med 2006;130:303-17. [Crossref] [PubMed]
16. Greer MD, Shih JH, Lay N, et al. Validation of the Dominant Sequence Paradigm and Role of Dynamic Contrast-enhanced Imaging in PI-RADS Version 2. Radiology 2017;285:859-69. [Crossref] [PubMed]
17. Pfau A. The treatment of chronic bacterial prostatitis. Infection 1991;19:S160-4. [Crossref] [PubMed]
18. Mathisen W, Normann E, Taksdal S, et al. Doxycycline levels in prostatic tissue and blood. Eur Urol 1975;1:157-8. [Crossref] [PubMed]
19. Pronk MJ, Pelger RC, Baranski AG, et al. Cure of chronic prostatitis presumably due to Enterococcus spp and gram-negative bacteria. Eur J Clin Microbiol Infect Dis 2006;25:270-1. [Crossref] [PubMed]
20. Le B, Schaeffer AJ. Chronic prostatitis. BMJ Clin Evid 2011;2011:1802. [PubMed]
21. Erickson BA, Schaeffer AJ, Van Le B. Chronic prostatitis. BMJ Clin Evid 2008;2008:1802. [PubMed]
22. Bowen DK, Dielubanza E, Schaeffer AJ. Chronic bacterial prostatitis and chronic pelvic pain syndrome. BMJ Clin Evid 2015;2015:1802. [PubMed]
23. Zasieda Y, Solomianyi R. Chronic prostatitis therapy combined with electromyostimulation-aspiration, transurethral electrophonophoresis of platelet-rich plasma and transrectal low-intensity pulsed ultrasound. Georgian Med News 2020;29-33. [PubMed]
24. Wagenlehner FM, Lunz JC, Kees F, et al. Serum and prostatic tissue concentrations of moxifloxacin in patients undergoing transurethral resection of the prostate. J Chemother 2006;18:485-9. [Crossref] [PubMed]
25. Boerema JB, Bach D, Jol C, et al. Penetration of rufloxacin into human prostatic tissue and fluid. J Antimicrob Chemother 1991;28:547-54. [Crossref] [PubMed]
26. Cunha BA, Gran A, Raza M. Persistent extended-spectrum β-lactamase-positive Escherichia coli chronic prostatitis successfully treated with a combination of fosfomycin and doxycycline. Int J Antimicrob Agents 2015;45:427-9. [Crossref] [PubMed]
27. Baumueller A, Hoyme U, Madsen PO. Rosamicin--a new drug for the treatment of bacterial prostatitis. Antimicrob Agents Chemother 1977;12:240-2. [Crossref] [PubMed]
28. Netto NR Jr, Palma PC, Srulzon GB, et al. Concentrations of norfloxacin in prostatic tissues following oral administration in patients with benign prostatic hyperplasia. Int Urol Nephrol 1988;20:47-9. [Crossref] [PubMed]
29. Lundy SD, Shoskes DA. (Mis)-Diagnosis and (Mis)-Management of Prostate Infections. AUA Update series. 2021; 40 (Lesson 28). Available online: https://auau.auanet.org/content/update-series-2021-lesson-28-mis-diagnosis-and-mis-management-prostate-infections#group-tabs-node-course-default2
30. Anothaisintawee T, Attia J, Nickel JC, et al. Management of chronic prostatitis/chronic pelvic pain syndrome: a systematic review and network meta-analysis. JAMA 2011;305:78-86. [Crossref] [PubMed]
31. Ateya A, Fayez A, Hani R, et al. Evaluation of prostatic massage in treatment of chronic prostatitis. Urology 2006;67:674-8. [Crossref] [PubMed]