Medicine:Chronic bacterial prostatitis

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Short description: Bacterial infection of the prostate gland
Chronic bacterial prostatitis
Other namesCBP

Chronic bacterial prostatitis (CBP) is a bacterial infection of the prostate gland and a form of prostatitis (prostate inflammation). It should be distinguished from other forms of prostatitis such as acute bacterial prostatitis (ABP) and chronic pelvic pain syndrome (CPPS).[1]

Signs and symptoms

Chronic bacterial prostatitis is a relatively rare condition that usually presents with an intermittent UTI-type picture. It is defined as recurrent urinary tract infections in men originating from a chronic infection in the prostate. Symptoms may be completely absent until there is also bladder infection, and the most troublesome problem is usually recurrent cystitis.[2] It has been said that recurrent and relapsing UTIs (i.e., UTIs due to the same pathogen) are a hallmark of chronic bacterial prostatitis.[3][4][5]


Dr. Weidner, Professor of Medicine, Department of Urology, University of Gießen, has stated: "In studies of 656 men, we seldom found chronic bacterial prostatitis. It is truly a rare disease. Most of those were E-coli."[6]

Causes

Chronic bacterial prostatitis is thought to be caused by ascending urethral infection and by reflux into the ejaculatory duct or prostatic ducts.[7] Risk factors for chronic bacterial prostatitis include functional or anatomic abnormalities, catheterization, prostate biopsy or urethritis (due to sexually transmitted infections), and unprotected penetrative anal sex.[7] In theory, the ability of some strains of bacteria to form biofilms might be one of the factors that facilitate the development of chronic bacterial prostatitis.[8] Recurrent infections may be caused by inefficient urination (benign prostatic hyperplasia, neurogenic bladder), prostatic stones, or a structural abnormality that acts as a reservoir for infection.

Diagnosis

In chronic bacterial prostatitis, there are bacteria in the prostate, but there may be no symptoms or milder symptoms than occur with acute prostatitis.[9] The prostate infection is diagnosed by culturing urine as well as prostate fluid (expressed prostatic secretions or EPS) which are obtained by the doctor performing a rectal exam and putting pressure on the prostate. If no fluid is recovered after this prostatic massage, a post massage urine should also contain any prostatic bacteria. Prostate specific antigen levels may be elevated, although there is no malignancy. Semen analysis is a useful diagnostic tool.[10] Semen cultures are also performed. Antibiotic sensitivity testing is also done to select the appropriate antibiotic. Other useful markers of infection are seminal elastase and seminal cytokines.

Treatment

Curative therapy

Antibiotics

Antibiotics are effective in the treatment of chronic bacterial prostatitis and are a first-line therapy for the condition.[11] A blood–prostate barrier exists that prevents many antibiotics from penetrating the prostate and achieving adequate antibacterial concentrations.[12][13][14] As such, only certain classes of antibiotics are effective and recommended for treatment of chronic bacterial prostatitis.[11][15] These include fluoroquinolones like ciprofloxacin and levofloxacin; trimethoprim; tetracyclines like doxycycline; and macrolides like azithromycin and clarithromycin.[11][15][16][17] Fluoroquinolones are the first-line antibiotics for chronic bacterial prostatitis, whereas trimethoprim and tetracyclines are second-line antibiotics and azithromycin is reserved for special situations.[11][15] Fosfomycin has also been repurposed for chronic bacterial prostatitis and is increasingly being employed in its treatment.[15][18][16] Antibiotic therapy of chronic bacterial prostatitis requires prolonged antibiotic courses of generally 4 to 6 weeks of treatment, but with a range of 2 to 12 weeks of therapy and a minimum recommended duration of 4 weeks of treatment.[11][15][7][17] A high dosage of levofloxacin for 2 or 3 weeks has been shown to be clinically inferior to a standard dosage of levofloxacin for 4 weeks.[15][19][20] Microbiological eradication rates with standard antibiotic therapy for chronic bacterial prostatitis have ranged from 40 to 77% for ciprofloxacin, 75 to 86% for levofloxacin, 77% for doxycycline, 80% for azithromycin, 80% for clarithromycin, and 62 to 77% for a combination of ciprofloxacin and azithromycin.[11][21] Although antibiotics are effective in the curative treatment of chronic bacterial prostatitis, recurrence rates are high and range from 25 to 50%.[22]

Levofloxacin (the levorotatory enantiomer of ofloxacin) has been found to reach prostatic fluid concentrations that are 5.5 times higher than those of the same dose of ciprofloxacin.[23][24][25] These findings indicate that levofloxacin has a greater ability to penetrate the prostate than ciprofloxacin and suggest that it might be comparatively more effective in the treatment of chronic bacterial prostatitis.[23][24][25] However, clinical findings have been mixed, with one large clinical trial finding that levofloxacin was more effective than ciprofloxacin (bacterial eradication rate = 86% vs. 60%; clinical cure/improvement = 93% vs. 72%; bacterial recurrence rate = 4% vs. 19%) and another similarly large trial finding that they were equivalent (bacterial eradication rate = 75% vs. 77%; clinical cure/improvement = 75% vs. 73%).[11][23][21][26] Moxifloxacin shows even greater prostatic penetration than levofloxacin as well as a broader spectrum of antibacterial activity, with improved activity against Gram-positive bacteria and anaerobic pathogens.[16][22] It may be the only fluoroquinolone able to obtain prostatic concentrations that are 10-fold above the minimum inhibitory concentration (MIC) against Enterococcus faecalis.[22] However, limited experience with and data on moxifloxacin for chronic bacterial prostatitis are available as of 2022.[22][16] Another limitation of moxifloxacin for such purposes is that it may have greater safety concerns than other fluoroquinolones, for instance higher cardiovascular risks.[16] Other fluoroquinolones that have also been used and found effective in the treatment of chronic bacterial prostatitis include norfloxacin, lomefloxacin, ofloxacin, and prulifloxacin.[27][16]

Aside from fluoroquinolones, certain other antibiotics with the potential for improved activity, including minocycline, tigecycline, linezolid, daptomycin, clindamycin, and vancomycin, have also been used limitedly off-label in the treatment of chronic bacterial prostatitis with reported success.[16][15][27][17] However, the safety of novel antibiotics for treatment of chronic bacterial prostatitis is understudied and significant toxicities are known for many of them, which is especially of concern due to the long treatment courses required.[16] Antibiotics with poor prostatic penetration that may not be suitable for curative treatment of chronic bacterial prostatitis include nitrofurantoin,[19][28][18][12][29] sulfamethoxazole, most penicillins (e.g., ampicillin, penicillin G), aminoglycosides, most cephalosporins, other β-lactams, and the tetracycline oxytetracycline, among others.[7][12][16][29] Findings on the penetration of amoxicillin into the prostate are inconsistent, with prostate tissue levels of 0.77 and 26.4 μg/mL reported in two different studies.[12][30] Clinical findings of amoxicillin/clavulanic acid for treatment of chronic bacterial prostatitis are also mixed, with reports of high rates of both success[28][31][32] and failure.[33][34] The more lipophilic tetracyclines minocycline and doxycycline show good or excellent prostate penetration like ciprofloxacin.[29][12][35] In smaller clinical studies, minocycline has been found to be equivalent or superior to doxycycline in the treatment of chronic bacterial prostatitis,[36][37] equivalent to trimethoprim/sulfamethoxazole,[38][39] and superior to the first-generation cephalosporin cephalexin.[17][27][40] It was also equivalent to the fluoroquinolone ofloxacin in the treatment of chronic bacterial prostatitis caused by Ureaplasma urealyticum.[27][41]

Prostatectomy

In some men, chronic bacterial prostatitis can be severe and highly refractory to treatment or relapsing.[42][43] In addition, it can be life-threatening due to urinary tract infections (UTIs).[43] Prostatectomy, or prostate removal surgery, has been used rarely and in well-selected patients to treat these kinds of cases.[42][43] A 2017 systematic review evaluated prostatectomy for chronic prostatitis.[42] Transurethral resection of the prostate (TURP) by electrocautery was done in 110 patients, and in these individuals, symptoms were cured in 70%, improved in 15%, and unchanged in 15%.[42] Radical prostatectomy was done in 21 patients and resulted in symptoms being cured in 95%.[42] There are significant rates of erectile dysfunction and urinary incontinence with prostatectomy.[42][43] These complications can be reduced with minimally invasive and nerve-sparing surgical techniques, such as robotically assisted radical prostatectomy or laparoscopic prostatectomy.[42][43] However, significant rates of complications still occur even with minimally invasive forms of prostatectomy.[42][43] All of the studies in the 2017 systematic review were prospective or retrospective case series and there were no randomized controlled trials.[42] As such, little evidence is available to inform clinical decision-making in terms of prostatectomy for chronic prostatitis.[42]

Other treatments

The addition of prostate massage to courses of antibiotics was previously proposed as being beneficial and prostate massage may mechanically break up the biofilm and enhance the drainage of the prostate gland.[44][45] However, in more recent trials, this was not shown to improve outcome compared to antibiotics alone.[46]

Bacteriophages hold promise as another potential treatment for chronic bacterial prostatitis.[7][47]

Symptomatic and suppressive therapy

Persistent infections may be helped in 80% of patients by the use of alpha blockers (α1-adrenergic receptor antagonists) or by long-term low-dose antibiotic therapy.[11][19][48] Alpha blockers, including tamsulosin, alfuzosin, and doxazosin among others, are used specifically in the management of voiding lower urinary tract symptoms (LUTS) like slow urinary flow or urinary hesitancy, although they might also help with pain and other symptoms.[11] However, their effectiveness is modest and the clinical significance has been questioned.[11] Possibilities for low-dose suppressive antibiotic therapy include nitrofurantoin, trimethoprim/sulfamethoxazole, fluoroquinolones, cephalosporins, and tetracyclines.[19][48] Prostate-penetrant nonsteroidal anti-inflammatory drugs (NSAIDs), like celecoxib and rofecoxib, as well as possibly ibuprofen, naproxen, and diclofenac, can also be used as analgesics to treat pain and inflammation in chronic bacterial prostatitis.[7][49]

Methenamine is a urinary antiseptic and antibacterial agent which is used in the prevention of recurrent urinary tract infections (UTIs).[50] It is non-inferior to low-dose prophylactic antibiotics for this purpose.[51][52][53] In contrast however, methenamine itself is not an antibiotic and does not promote antibiotic resistance.[50][51] The drug works by being selectively and pH-dependently decomposed in acidic environments like the bladder into the active form formaldehyde, which is potently bactericidal.[50] Since formaldehyde is only formed from methenamine in acidic environments, it is not expected to be effective in the curative treatment of chronic bacterial prostatitis, and hence is not recommended for such purposes.[50] Methenamine decomposes into formaldehyde at a pH of below 6,[50] whereas the normal pH of prostatic fluid is 6.5 to 6.7 and in chronic prostatitis the pH is 7.0 to 8.3.[12] However, in persistent chronic bacterial prostatitis, prophylactic methenamine may be useful as an alternative to low-dose prophylactic antibiotics in preventing prostatitis-derived UTIs and managing associated symptoms.[19] Prophylactic low-dose methenamine combined with an ascorbic acid (vitamin C) supplement, which is theorized to enhance its activity by making the urine more acidic, has been reported to be effective for this purpose based on clinical experience.[19] In any case, supporting clinical data for this use are lacking as of 2020.[19]

Androgen deprivation therapy with surgical castration, estrogens, and the 5α-reductase inhibitor finasteride have shown beneficial effects on chronic bacterial prostatitis in terms of bacterial growth and inflammation in animal models, but clinical studies in humans have not been performed.[22][54][55]

Prognosis

Over time, the relapse rate is high, exceeding 50%. However, recent research indicates that combination therapies offer a better prognosis than antibiotics alone.

A 2007 study showed that repeated combination pharmacological therapy with antibacterial agents (ciprofloxacin/azithromycin), alpha-blockers (alfuzosin) and Serenoa repens extracts may eradicate infection in 83.9% of patients with clinical remission extending throughout a follow-up period of 30 months for 94% of these patients.[56]

A 2014 study of 210 patients randomized into two treatment groups found that recurrence occurred within 2 months in 27.6% of the group using antibiotics alone (prulifloxacin 600 mg), but in only 7.8% of the group taking prulifloxacin in combination with Serenoa repens extract, Lactobacillus sporogens (now Heyndrickxia coagulans), and arbutin (a combination referred to by the name "Lactorepens").[57]

Large prostatic stones was shown to be related with the presence of bacteria,[58] a higher urinary symptoms and pain score, a higher IL-1β and IL-8 concentration in seminal plasma, a greater prostatic inflammation and a lower response to antibiotic treatment.[59]

Epidemiology

In a 2008 systematic review of 10,617 men, 8.2% had experienced prostatitis symptoms.[11][60] It has been estimated that 35 to 50% of men may be affected by prostatitis symptoms during their lifetime.[11]

Additional images

  • Prostate, urethra, and seminal vesicles.
    Prostate, urethra, and seminal vesicles.
  • The arteries of the pelvis.
    The arteries of the pelvis.
  • Male pelvic organs seen from right side.
    Male pelvic organs seen from right side.

References

  1. ↑ "Common Questions About Chronic Prostatitis". American Family Physician 93 (4): 290–6. February 2016. PMID 26926816. 
  2. ↑ "Prostatitis/chronic pelvic pain syndrome". Annual Review of Medicine 57 (1): 195–206. 2006. doi:10.1146/annurev.med.57.011205.135654. PMID 16409145. 
  3. ↑ "Approach to urinary tract infections". Indian J Nephrol 19 (4): 129–39. October 2009. doi:10.4103/0971-4065.59333. PMID 20535247. 
  4. ↑ "Treatment of bacterial prostatitis". Clin Infect Dis 50 (12): 1641–52. June 2010. doi:10.1086/652861. PMID 20459324. 
  5. ↑ "Prostatic fluid inflammation in prostatitis". J Urol 152 (6 Pt 2): 2300–3. December 1994. doi:10.1016/s0022-5347(17)31662-2. PMID 7966728. 
  6. ↑ "The 2001 Giessen Cohort Study on patients with prostatitis syndrome--an evaluation of inflammatory status and search for microorganisms 10 years after a first analysis". Andrologia 35 (5): 258–62. October 2003. doi:10.1046/j.1439-0272.2003.00586.x. PMID 14535851. 
  7. ↑ 7.0 7.1 7.2 7.3 7.4 7.5 "Pharmacotherapeutic interventions for the treatment of bacterial prostatitis". Expert Opin Pharmacother 23 (9): 1091–1101. June 2022. doi:10.1080/14656566.2022.2077101. PMID 35574695. 
  8. ↑ "Bacterial prostatitis". World Journal of Urology 31 (4): 711–6. August 2013. doi:10.1007/s00345-013-1055-x. PMID 23519458. 
  9. ↑ "Prostatitis - Symptoms". NHS Choices. 2017-10-19. http://www.nhs.uk/Conditions/Prostatitis/Pages/Introduction.aspx. 
  10. ↑ "Semen analysis in chronic bacterial prostatitis: diagnostic and therapeutic implications". Asian Journal of Andrology 11 (4): 461–77. July 2009. doi:10.1038/aja.2009.5. PMID 19377490. 
  11. ↑ 11.00 11.01 11.02 11.03 11.04 11.05 11.06 11.07 11.08 11.09 11.10 11.11 "Diagnosis and treatment of chronic bacterial prostatitis and chronic prostatitis/chronic pelvic pain syndrome: a consensus guideline". BJU Int 116 (4): 509–525. October 2015. doi:10.1111/bju.13101. PMID 25711488. 
  12. ↑ 12.0 12.1 12.2 12.3 12.4 12.5 "Penetration of antimicrobial agents into the prostate". Chemotherapy 49 (6): 269–279. December 2003. doi:10.1159/000074526. PMID 14671426. http://home.swipnet.se/isop/Penetration.pdf. "Good to excellent penetration into prostatic fluid and tissue has been demonstrated with many antimicrobial agents, including tobramycin, netilmicin, tetracyclines, macrolides, quinolones, sulfonamides and nitrofurantoin. [...] Nitrofurantoin is a lipid-soluble weak acid with a pKa value that is somewhat favorable for diffusion into prostatic fluid [78]. Although low levels of nitrofurantoin were achieved in prostatic fluid in dogs, the administration of standard oral doses of this drug to men results in levels of ≤1 μg/ml of blood; such levels guarantee that the levels attained in prostatic fluid will be nontherapeutic.". 
  13. ↑ "A blood-prostate barrier restricts cell and molecular movement across the rat ventral prostate epithelium". The Journal of Urology 163 (5): 1591–1594. May 2000. doi:10.1016/S0022-5347(05)67685-9. PMID 10751894. http://www.jurology.com/article/S0022-5347%2805%2967685-9/abstract. 
  14. ↑ "Anatomical barriers for antimicrobial agents". European Journal of Clinical Microbiology & Infectious Diseases 12 (Suppl 1): S31–S35. January 1993. doi:10.1007/BF02389875. PMID 8477760. 
  15. ↑ 15.0 15.1 15.2 15.3 15.4 15.5 15.6 "How I manage bacterial prostatitis". Clin Microbiol Infect 29 (1): 32–37. January 2023. doi:10.1016/j.cmi.2022.05.035. PMID 35709903. "Duration of fluoroquinolone therapy appears to be more integral than antimicrobial dose. For instance, in patients with CBP, lower rates of clinical recurrence within 6-months following a 4-week course of levofloxacin 500 mg orally daily were reported compared to a 2- or 3-week course of levofloxacin 750 mg orally daily [45].". 
  16. ↑ 16.0 16.1 16.2 16.3 16.4 16.5 16.6 16.7 16.8 "Safety considerations with new antibacterial approaches for chronic bacterial prostatitis". Expert Opin Drug Saf 21 (2): 171–182. February 2022. doi:10.1080/14740338.2021.1956459. PMID 34260337. 
  17. ↑ 17.0 17.1 17.2 17.3 "Multidisciplinary approach to prostatitis". Arch Ital Urol Androl 90 (4): 227–248. January 2019. doi:10.4081/aiua.2018.4.227. PMID 30655633. "The antibiotic treatment of chronic prostatitis is currently based on the use of fluoroquinolones that, given for 2 to 4 weeks, cured about 70% of men with chronic bacterial prostatitis. [...] Tetracyclines, especially doxycycline and minocycline, and macrolides have been extensively used to treat CBP. In a RCT minocycline demonstrated better microbiological (45 vs 21%) and clinical (65 vs 46%) cure rates than cephalexin. [...] The optimal duration of antibiotic treatment for CBP has not been defined by controlled trials, although a study demonstrated the superiority of a 12 week TMP/SMX treatment with respect to a 10 day course of the same antimicrobial agent. However a minimum duration of antibiotic treatment of 4 weeks should be considered. In a RCT clinical success at the 6-month follow up of levofloxacin 750 mg/day for 2 or 3 weeks was inferior to the standard therapy with levofloxacin 500 mg/day for 4 weeks (71).". 
  18. ↑ 18.0 18.1 "Antimicrobial Treatment Options for Difficult-to-Treat Resistant Gram-Negative Bacteria Causing Cystitis, Pyelonephritis, and Prostatitis: A Narrative Review". Drugs 82 (4): 407–438. March 2022. doi:10.1007/s40265-022-01676-5. PMID 35286622. "We agree with guidelines [270] recommending fluoroquinolones, trimethoprim, and tetracyclines for treatment of chronic bacterial prostatitis, if the causative organism is susceptible. Emerging pharmacologic and clinical data also support the use of oral fosfomycin 3g every 2 days for 6–12 weeks for treatment of chronic bacterial prostatitis [256, 266, 271]. We avoid prescribing nitrofurantoin due to concerns of poor prostatic concentration [265].". 
  19. ↑ 19.0 19.1 19.2 19.3 19.4 19.5 19.6 "Management of Chronic Bacterial Prostatitis". Curr Urol Rep 21 (7): 29. June 2020. doi:10.1007/s11934-020-00978-z. PMID 32488742. "Chronic oral antibiotic suppression for men with persistent or recurrent prostatic infections despite antibiotic treatment is frequently used in clinical practice, even though supporting data are presently lacking [2, 18]. This approach appears to be generally effective, so long as suppression can be maintained [17]. Suitable choices include nitrofurantoin, trimethoprim-sulfamethoxazole, methenamine, fluoroquinolones, cephalosporins, tetracyclines, or any agent previously effective for the isolated pathogen. [...] In our experience, many patients who previously struggled with symptomatic recurrences have been well controlled with chronic low-dose prophylaxis with methenamine combined with a vitamin C supplement. However, the long-term utility of prophylaxis with methenamine therapy is not well documented in the existing literature [60].". 
  20. ↑ "Safety and efficacy of levofloxacin 750 mg for 2 weeks or 3 weeks compared with levofloxacin 500 mg for 4 weeks in treating chronic bacterial prostatitis". Curr Med Res Opin 26 (6): 1433–1441. June 2010. doi:10.1185/03007991003795030. PMID 20394471. 
  21. ↑ 21.0 21.1 "Safety and efficacy of levofloxacin versus ciprofloxacin for the treatment of chronic bacterial prostatitis in Chinese patients". Asian J Androl 14 (6): 870–874. November 2012. doi:10.1038/aja.2012.48. PMID 22864282. 
  22. ↑ 22.0 22.1 22.2 22.3 22.4 "Pharmacological Interventions for Bacterial Prostatitis". Front Pharmacol 11: 504. 2020. doi:10.3389/fphar.2020.00504. PMID 32425775. 
  23. ↑ 23.0 23.1 23.2 "Levofloxacin in the treatment of urinary tract infections and prostatitis". J Chemother 16 Suppl 2: 18–21. April 2004. doi:10.1080/1120009x.2004.11782369. PMID 15255558. 
  24. ↑ 24.0 24.1 "Levofloxacin and its effective use in the management of bacterial prostatitis". Penetration: 21–26. 2009. http://www.infectweb.com/only/artsrv2009_1.pdf. Retrieved 2016-02-08. 
  25. ↑ 25.0 25.1 "Limitations in the Use of drug cocktails (DC) to compare pharmacokinetics (PK) of drugs: ciprofloxacin (CIP) vs. levofloxacin (LEV) [poster No. 506"]. 40th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC); September 17–20, 2000; Toronto, Canada. 2000. https://scholar.google.com/scholar?cluster=6314753989545991945. 
  26. ↑ "Levofloxacin versus ciprofloxacin in the treatment of chronic bacterial prostatitis: a randomized double-blind multicenter study". Urology 62 (3): 537–541. September 2003. doi:10.1016/s0090-4295(03)00565-x. 
  27. ↑ 27.0 27.1 27.2 27.3 "Antimicrobial therapy for chronic bacterial prostatitis". Cochrane Database Syst Rev 2013 (8). August 2013. doi:10.1002/14651858.CD009071.pub2. PMID 23934982. 
  28. ↑ 28.0 28.1 "Treatment of bacterial prostatitis". Clin Infect Dis 50 (12): 1641–1652. June 2010. doi:10.1086/652861. PMID 20459324. "Nitrofurantoin prostatic levels are likely nontherapeutic.". 
  29. ↑ 29.0 29.1 29.2 "Tetracyclines in urology: current concepts". Urology 36 (6): 548–556. December 1990. doi:10.1016/0090-4295(90)80201-w. PMID 2247929. 
  30. ↑ "Enterococcus faecalis-related prostatitis successfully treated with moxifloxacin". Antimicrob Agents Chemother 59 (11): 7156–7157. November 2015. doi:10.1128/AAC.01988-15. PMID 26349832. "The treatment of enterococcal prostatitis remains a challenge because of the paucity of antibiotics achieving both bactericidal effect and good prostatic diffusion. Indeed, prostatic concentrations of amoxicillin have not been consistently assessed, with concentrations varying from 0.77 to 26 μg/ml (2).". 
  31. ↑ "Chronic bacterial prostatitis and chronic pelvic pain syndrome". BMJ Clin Evid 2015. August 2015. PMID 26313612. "Amoxicillin-clavulanic acid (co-amoxiclav) and clindamycin. One case series included 50 men resistant to empirical treatment with quinolones. The expressed prostatic secretions from 24 of these men exhibited high colony counts of gram-positive and gram-negative anaerobic bacteria, either alone (18 men) or in combination with aerobic bacteria (6 men). After treatment with either amoxicillin-clavulanic acid or clindamycin for 3 to 6 weeks, all men had a decrease or total elimination of symptoms, and no anaerobic bacteria were detected in prostatic secretions.". 
  32. ↑ "The possible role of anaerobic bacteria in chronic prostatitis". Int J Androl 21 (3): 163–168. June 1998. doi:10.1111/j.1365-2605.1998.00110.x. PMID 9669200. "Patients with chronic prostatitis who gave positive culture results for anaerobes were treated with amoxicillin/clavulanic acid or clindamycin for 3-6 weeks. After treatment, samples were again taken and cultured for all pathogens known to cause prostatitis. These post-therapeutic samples revealed a decrease or total elimination of the symptoms, and no anaerobic bacteria could be detected.". 
  33. ↑ "Bacterial prostatitis". Urologic Clinics of North America 35 (1): 23–32; v. February 2008. doi:10.1016/j.ucl.2007.09.008. PMID 18061021. "Although penicillin derivatives have a reported role in the treatment of acute bacterial prostatitis, one study found that no patients treated with amoxicillin/clavulanic acid had resolution of their prostatitis [7,60].". 
  34. ↑ "Use of prostatic massage in combination with antibiotics in the treatment of chronic prostatitis". Prostate Cancer Prostatic Dis 2 (3): 159–162. May 1999. doi:10.1038/sj.pcan.4500308. PMID 12496826. "In the NIH category II patients, there was no correlation between type of organism isolated or antibiotic used with response to therapy with the exception that no patient treated with [amoxicillin]–clavulonic acid had a complete and durable response.". 
  35. ↑ "Minocycline". Ther Drug Monit 4 (2): 137–145. 1982. doi:10.1097/00007691-198206000-00002. PMID 7048646. https://journals.lww.com/drug-monitoring/abstract/1982/06000/Minocycline.2.aspx. 
  36. ↑ "Minocycline: old and new therapeutic uses". Int J Antimicrob Agents 4 (4): 325–335. 1994. doi:10.1016/0924-8579(94)90034-5. PMID 18611625. "Clinical evaluation was used to compare the effectiveness of minocycline in prostatitis with that of doxycycline [40], cotrimoxazole [41,42], trimethoprim [42], and cephalexin [43]. Standard doses of all antibiotics were employed in these studies, with minocycline being administered orally or IV as a 200 mg loading dose followed by 100 mg twice daily. In all cases, minocycline was found to be as good or better than the comparative agent(s).". 
  37. ↑ "Treatment of chronic prostatitis. Comparison of Minocycline and Doxycycline". Urology 5 (5): 626–631. May 1975. doi:10.1016/0090-4295(75)90114-4. PMID 1093309. 
  38. ↑ "Chronic bacterial prostatitis: theoretical and experimental considerations". Urol Res 11 (1): 1–5. 1983. doi:10.1007/BF00272700. PMID 6344395. "In a recent clinical study, trimethoprim-sulfamethoxazole and minocycline were found equally effective [34], while Ristuccia and Cunha chose doxycycline for the treatment of chronic bacterial prostatis because of its ability to penetrate the prostate, its broad antibacterial spectrum including chlamydia and its few side effects [35].". 
  39. ↑ "Trimethoprium-sulfamethoxazole and minocycline- hydrochloride in the treatment of culture-proved bacterial prostatitis". J Urol 120 (2): 184–185. August 1978. doi:10.1016/s0022-5347(17)57096-2. PMID 671629. 
  40. ↑ "Treatment of bacterial prostatitis. Comparison of cephalexin and minocycline". Urology 27 (4): 379–387. April 1986. doi:10.1016/0090-4295(86)90321-3. PMID 3515737. 
  41. ↑ "Antimicrobial treatment for chronic prostatitis as a means of defining the role of Ureaplasma urealyticum". Urol Int 51 (3): 129–132. 1993. doi:10.1159/000282530. PMID 8249222. 
  42. ↑ 42.00 42.01 42.02 42.03 42.04 42.05 42.06 42.07 42.08 42.09 "Surgical therapy of prostatitis: a systematic review". World J Urol 35 (11): 1659–1668. November 2017. doi:10.1007/s00345-017-2054-0. PMID 28612108. 
  43. ↑ 43.0 43.1 43.2 43.3 43.4 43.5 "Surgical management of National Institutes of Health category II chronic bacterial prostatitis: a case series and scoping review of the literature". Transl Androl Urol 12 (10): 1581–1588. October 2023. doi:10.21037/tau-23-142. PMID 37969767. 
  44. ↑ "Repetitive prostatic massage therapy for chronic refractory prostatitis: the Philippine experience". Techniques in Urology 5 (3): 146–51. September 1999. PMID 10527258. 
  45. ↑ "Use of prostatic massage in combination with antibiotics in the treatment of chronic prostatitis". Prostate Cancer and Prostatic Diseases 2 (3): 159–162. May 1999. doi:10.1038/sj.pcan.4500308. PMID 12496826. 
  46. ↑ "Evaluation of prostatic massage in treatment of chronic prostatitis". Urology 67 (4): 674–8. April 2006. doi:10.1016/j.urology.2005.10.021. PMID 16566972. 
  47. ↑ "The perspectives of the application of phage therapy in chronic bacterial prostatitis". FEMS Immunology and Medical Microbiology 60 (2): 99–112. November 2010. doi:10.1111/j.1574-695X.2010.00723.x. PMID 20698884. 
  48. ↑ 48.0 48.1 "Long-term results of multimodal therapy for chronic prostatitis/chronic pelvic pain syndrome". The Journal of Urology 169 (4): 1406–10. April 2003. doi:10.1097/01.ju.0000055549.95490.3c. PMID 12629373. 
  49. ↑ "Interventions to chronic prostatitis/Chronic pelvic pain syndrome treatment. Where are we standing and what's next?". European Journal of Pharmacology 857. August 2019. doi:10.1016/j.ejphar.2019.172429. PMID 31170381. 
  50. ↑ 50.0 50.1 50.2 50.3 50.4 "Methenamine: a forgotten drug for preventing recurrent urinary tract infection in a multidrug resistance era". Expert Rev Anti Infect Ther 12 (5): 549–554. May 2014. doi:10.1586/14787210.2014.904202. PMID 24689705. 
  51. ↑ 51.0 51.1 "An oldie but a goodie: Methenamine as a nonantibiotic solution to the prevention of recurrent urinary tract infections". PLOS Pathog 19 (6). June 2023. doi:10.1371/journal.ppat.1011405. PMID 37319137. 
  52. ↑ "Methenamine for urinary tract infection prophylaxis: A systematic review". Pharmacotherapy 44 (2): 197–206. February 2024. doi:10.1002/phar.2895. PMID 37986168. 
  53. ↑ "Use of Methenamine for Urinary Tract Infection Prophylaxis: Systematic Review of Recent Evidence". Int Urogynecol J 35 (3): 483–489. March 2024. doi:10.1007/s00192-024-05726-2. PMID 38329493. 
  54. ↑ "Does finasteride have a preventive effect on chronic bacterial prostatitis? Pilot study using an animal model". Urol Int 86 (2): 204–209. 2011. doi:10.1159/000320109. PMID 21273757. 
  55. ↑ "Effects of androgen deprivation on chronic bacterial prostatitis in a rat model". Int J Urol 10 (9): 485–491. September 2003. doi:10.1046/j.1442-2042.2003.00666.x. PMID 12941127. 
  56. ↑ "Efficacy of repeated cycles of combination therapy for the eradication of infecting organisms in chronic bacterial prostatitis". International Journal of Antimicrobial Agents 29 (5): 549–56. May 2007. doi:10.1016/j.ijantimicag.2006.09.027. PMID 17336504. 
  57. ↑ "Chronic bacterial prostatitis: efficacy of short-lasting antibiotic therapy with prulifloxacin (Unidrox®) in association with saw palmetto extract, lactobacillus sporogens and arbutin (Lactorepens®)". BMC Urology 14 (1): 53. July 2014. doi:10.1186/1471-2490-14-53. PMID 25038794. 
  58. ↑ Mazzoli, Sandra (August 2010). "Biofilms in chronic bacterial prostatitis (NIH-II) and in prostatic calcifications". FEMS Immunology and Medical Microbiology 59 (3): 337–344. doi:10.1111/j.1574-695X.2010.00659.x. ISSN 1574-695X. PMID 20298500. 
  59. ↑ Soric, Tomislav; Selimovic, Mirnes; Bakovic, Lada; Šimurina, Tatjana; Selthofer, Robert; Dumic, Jerka (2017). "Clinical and Biochemical Influence of Prostatic Stones". Urologia Internationalis 98 (4): 449–455. doi:10.1159/000455161. ISSN 1423-0399. PMID 28052296. 
  60. ↑ "Epidemiology of prostatitis". Int J Antimicrob Agents 31 Suppl 1 (Suppl 1): S85–S90. February 2008. doi:10.1016/j.ijantimicag.2007.08.028. PMID 18164907. 
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