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COMBINATION REGIMEN IN THE TREATMENT OF CHRONIC PROSTATITIS W. -M. Chen a; C. -R. Yang a; Y. -C. Ou a; H. -C. Ho a; C. -K. Su a; K. -Y. Chiu a; C. -L. Cheng a a Division of Urology, Department of Surgery, Taichung Veterans General Hospital, National Yang-Ming University School of Medicine, Taipei, Taiwan, Republic of China Online Publication Date: 01 March 2006
To cite this Article Chen, W. -M., Yang, C. -R., Ou, Y. -C., Ho, H. -C., Su, C. -K., Chiu, K. -Y. and Cheng, C. -L.(2006)'COMBINATION
REGIMEN IN THE TREATMENT OF CHRONIC PROSTATITIS',Systems Biology in Reproductive Medicine,52:2,117 — 121 To link to this Article: DOI: 10.1080/01485010500316113 URL: http://dx.doi.org/10.1080/01485010500316113
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Archives of Andrology, 52:117–121, 2006 Copyright # Taylor & Francis Group, LLC ISSN: 0148-5016 print/1521-0375 online DOI: 10.1080/01485010500316113
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COMBINATION REGIMEN IN THE TREATMENT OF CHRONIC PROSTATITIS
W.-M. Chen, C.-R. Yang, Y.-C. Ou, H.-C. Ho, C.-K. Su, K.-Y. Chiu, and C.-L. Cheng & Division of Urology, Department of Surgery, Taichung Veterans General Hospital, National Yang-Ming University School of Medicine, Taipei, Taiwan, Republic of China
& The aim of the study was to report our experiences in the treatment of chronic prostatitis using combination regimen including ciprofloxacin, doxazosin, allopurinol and biofeedback perineal massage. From May 2003 to April 2004, 7 patients with NIH Category II-chronic bacterial prostatitis and 7 patients with NIH Category IIIA-inflammatory chronic pelvic pain syndrome were treated. The NIH-Chronic Prostatitis Symptom Index (NIH-CPSI) was scored by the patient before and after the treatment, 6 months later. In Category II patients, the bacterial eradication rate was 71% after ciprofloxacin treatment during a follow-up of 6 months. The beneficial response rate to allopurinol, doxazosin and biofeedback perineal massage was 50%, 42% and 85%, respectively. In NIH Category IIIA patients, the individual beneficial response rate to ciprofloxacin, allopurinol, doxazosin and biofeedback perineal massage was 57%, 100%, 71% and 100%, respectively. Comparing pre-treatment and post-treatment results of the combination regimen, there was a statistically significant improvement in the 3 domains of pain score, urinary symptoms and quality of life impact of the NIH-CPSI. Combination regimen including ciprofloxacin, doxazosin allopurinol and biofeedback perineal massage in the treatment of chronic prostatitis is a safe and effective modality in our limited experience. Keywords chronic bacterial prostatitis, inflammatory chronic pelvic pain syndrome
Chronic prostatitis is a condition that causes men substantial morbidity through the associated problems of urinary symptoms, sexual dysfunction, and pelvic pain [10–14]. It consumes a significant proportion of the office time of the busy urologist. The source of these symptoms is still poorly understood, and the many and varied treatments for chronic prostatitis reflect in part this knowledge gap. The chronic form of the syndrome seems to be caused by possible infectious and noninfectious prostatitic Address correspondence to Chen-Li Cheng, M.D., Division of Urology, Department of Surgery, Taichung Veterans General Hospital, 160 Section 3, Taichung-Kang Rd., Taichung, Taiwan, R.O.C. E-mail: wmchen@vghtc.gov.tw
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inflammation as well as noninflammatory causes including the dysfunctional high-pressure voiding [8, 9], intraprostatic ductal reflux of urine and its metabolites (urate) irritation [16], autoimmune [5, 19] and neuromuscular spastic dysfunction [6, 18]. The Chronic Prostatitis Collaborative Research Network funded by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) developed and validated the NIH Chronic Prostatitis Symptom Index (CPSI) to measure the symptoms of chronic prostatitis. This index was easily stratified into the logical domains of pain, urinary symptoms, and impact on quality of life and had excellent internal consistency and high test-retest reliability [11]. MATERIAL AND METHODS The (NIH) classification system was used to classify the prostatitis syndromes [10]. The premassage and postmassage test (two-glass test) was used as the technique of lower urinary tract cytologic examination and culture [14]. Seven patients (25–71 yrs) with NIH category II-chronic bacterial prostattitis and 7 patients (33–62 yrs) with NIH category IIIAinflammatory pelvic pain syndrome were divided in 2 groups according to age culture results at expressed prostatic secretions (EPS) and presence or absence of urate crystal in postmassage urinary analysis. Patients completed self-administered questionnaire of NIH Chronic Prostatitis Symptom Index (CPSI) before and 6 months after treatment. In group I (NIH Category IIchronic bacterial prostatitis), patients received ciprofloxacin 250 mg bid for 8 weeks, allopurinol 100 mg qd for positive presentation of urate crystal in postmassage urinary analysis for 8 weeks and doxazosin 1 mg bid continuously. Patients were taught to perform the biofeedback perineal massage and asked to do the procedure daily at bedtime. Bacterial eradication rate was evaluated by the two-glass test and EPS culture again 6 months later after ciprofloxacin therapy. In group II (NIH category, IIA-inflammatory chronic pelvic pain syndrome), patients received ciprofloxacin 250 mg bid for 2 weeks initially. If the symptoms had improved, they received further 4 weeks antibiotic therapy. If the symptoms had not improved, the antibiotic was abandoned. The allopurinol, doxazosin and biofeedback perineal massage were administered in the same way as patients in group I. RESULTS In group I (NIH-category II) patients, the EPS cultures revealed E. coli in 2 patients, gram-positive enterococci in 3 patients and coagulase-negative staphylococci in 2 patients. In 5 of 7 patients, the pathogens were eradicated during follow-up of 6 months after ciprofloxacin therapy. Two
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patients had urate crystal in postmassage urinary analysis and 1 of 2 patients had beneficial response to allopurinol therapy. Three of 7 patients had beneficial response to doxazosin treatment. There was a statistically significant improvement in the domains of pain score and quality of life impact of the NIH-CPSI, but the urinary symptoms did not improved significantly. In sign group II (NIH Category IIIA) patients, 4 of 7 patients had good response to ciprofloxacin therapy and the antibiotic was given for 6 weeks. The WBC counts were zero in the postmassage urinary analysis of all 4 patients during follow-up of 6 months. Three patients had urate crystal in postmassage urinary analysis and all of them had beneficial response to allopurinol therapy. Five of seven patients had response to doxazosin treatment. All the patients (100%) had beneficial response to biofeedback perineal massage. There were significant improvements in the 3 domains of pain score, urinary symptoms and quality of life impact of the NIH-CPSI. During the period of the combination regimen treatment among these 14 patients, 2 patients complained of anorexia during ciprofloxacin therapy and 3 patients complained of dizziness during doxazosin therapy at the initial dose given. All the symptoms had subsided gradually in the clinical follow-up. There were complications of the allopurinol and biofeedback perineal massage therapies. DISCUSSION In lower urinary tract cytologic examination and culture techniques, the Meares-Stamey four-glass lower urinary tract localization test for chronic prostatitis has remained the gold standard [12, 24]. However, the test is considered time-consuming and expensive, so the majority of urologists and primary care physicians do not routinely employ the four-glass test [13]. This test had a 91% sensitivity and specificity compared with the gold standard Meares-Stamey test [14]. NIH-CPSI [5] which is very important to understand this syndrome, provides a valid outcome measure for chronic prostatitis. The acceptable penetration, distribution and concentration of ciprofloxacin in prostatic tissue and fluid has been reported [2, 4]. This antibiotic has been used widely in the treatment of chronic bacterial prostatitis [20–23]. In group I (NIH-category II) patients, the bacterial eradication rate was 71% during follow-up of 6 months. The result was similar to other studies with bacterial eradication rates of 60% to 80%.9 In group II (NIH-category IIIA) patients, 4 (57%) of 7 patients had beneficial effects after 6 weeks of ciprofloxacin therapy. Antibiotics may be effective in NIH-category IIIA patients for two reasons. First, the definition of culture-negative chronic prostatitis does not exclude the possibility of a bacterial cause, which may not be identifiable using our current standard microbiologic methodology [15]. Furthermore,
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antibiotics have a defined anti-inflammatory effect independent of their antibacterial action. Antibiotics, especially the quinolones, have an immunomodulatory action on inflammatory cytokines [7]. One model for the pathophysiology of chronic prostatitis suggests that habitual voluntary contraction or inability to properly relax the bladder neck or urethral sphincter leads to turbulent urinary flow, intraprostatic reflux, and chemically induced prostatic inflammation [16]. By relieving outflow obstruction, alpha-blockers may reduce the turbulent urinary flow and prostatic duct reflux, thus diminishing the likelihood of a chemically induced prostatic inflammation [1]. Doxazosin therapy in our study showed 42% improvement rate in group I patients and 71% response rate in group II patients. Patients with chronic prostatitis, especially patients with NIH-category IIIA, may have bladder outflow obstruction. Doxazosin relieves the dynamic outflow dysfunction. Pain associated with chronic tension and spasm of the pelvic floor muscles has been hypothesized to be a contributing factor in chronic prostatitis [6, 17, 18]. Biofeedbackassisted pelvic floor re-education has been used successfully to treat chronic pelvic pain syndrome [2, 3]. REFERENCES 1. Barbalias GA, Nikiforidis G, Liatsikos EN (1998): Alpha-blockers for the treatment of chronic prostatitis in combination with antibiotics. J Urol 159:883–887. 2. Boerema JB, Dalhoff A, Debruyne FMY (1985): Ciprofloxacin distribution in prostatic tissue and fluid following oral administration. Chemotherapy 31:13–18. 3. Clemens JQ, Nadler RB, et al. (2000): Biofeedback, pelvic floor re-education, and bladder training for male chronic pelvic pain syndrome. Urology 56:951–955. 4. Dalhoff A, Weidner W (1984): Diffusion of ciprofloxacin into prostatic fluid. Eur J Clin Microbiol 3:360–366. 5. Dobe A, Walker MM, et al. (1990): Intraprostatic antibody deposition in chronic abacterial prostatitis. Br J Urol 65:598–605. 6. Egan KJ, Krieger JL (1997): Chronic abacterial prostatitis—a urological chronic pain syndrome? Pain 69:213–218. 7. Galley HF, Nelson SJ, et al. (1997): Effect of ciprofloxacin on the accumulation of interleukin-6, interleukin-8, and nitrite from a human endothelial cell model of sepsis. Crit Care Med 25: 1392–1395. 8. Kaplan SA, Te AE, Jacobs BZ (1994): Urodynamic evidence of vesicle neck obstruction in men with misdiagnosed chronic nonbacterial prostatitis and the therapeutic role of endoscopic incision of the bladder neck. J Urol 152:2063–2065. 9. Kaplan SA, Santarosa RP, et al. (1997): Pseudodyssynergia (contraction of the external sphincter during voiding) misdiagnosed as chronic nonbacterial prostatitis and the role of biofeedback as a therapeutic option. J Urol 157:2234–2237. 10. Krieger JN, Nyberg LJ, Nickel JC (1999): NIH consensus definition and classification of prostatitis. JAMA 282:236–237. 11. Litwin MS, McNaughton-Collins M, et al. (1999): The national institutes of health chronic prostatitis symptom index: development and validation of a new outcome measure. J Urol 162:369–375. 12. Meares EM Jr, Stamey TA (1968): Bacteriologic localization patterns in bacterial prostatitis and urethritis. Invest Urol 5:492–518.
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