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Use of Antibiotics in Chronic Prostatitis Syndromes Daniel Shoskes MD, MSc, FRCS(C) Cleveland Clinic Florida Epidemiology of Chronic Prostatitis • Estimated prevalence 8-14% – Mehik A et al BJU Int 2000; 86 (4): 443 • Up to 50% of men treated for symptoms of prostatitis at least once in life • Sickness impact equivalent to MI, Crohn's or angina – Wenninger K et al J Urol 1996; 155 (3): 965. • Mental QOL impact equivalent to severe diabetes NIH Classification of Prostatitis • Category I – Acute Bacterial Prostatitis • Category II – Chronic Bacterial Prostatitis • Category III – Chronic Pelvic Pain Syndrome • Category IV – Asymptomatic Inflammation Category II Prostatitis • No controversy – recurrent UTI, uropathogen, EPS positive between attacks • Some controversy – no UTI, uropathogen localized to EPS • Much controversy – non-uropathogen localized to EPS – role of Staph, Strep, anaerobes, yeast, biofilm Culture of EPS and Semen • 202 patients in NIH study had 4 glass test + semen, cultured for 2 and 5 days • Significant proportion of cultures negative at 2 days were positive at 5 days (2-/5+) – VB1 14.6%, VB2 6.9%, EPS 23.3%, VB3 9.3% and semen 20% – Strep and Corynebacteria found in all samples – Staph and E. coli ONLY EPS, VB3 and Semen – 3 of 7 positive E. coli cultures in study were 2-/5+ – 63% of EPS and 52% of semen 2-/5+ were absent in VB1 or VB2 Antibiotic Selection in Prostatitis • high pKa, lipid soluble • primary concern for gram -ve, enterococcus • secondary concern for gram +ve, chlamydia, anaerobes • quinolones, macrolides, tetracyclines, sulphas • nitrofurantoin does NOT penetrate prostate Cipro for E. coli Chronic Prostatitis • 40 men, Cipro for 4 weeks • EPS sterilized in: – 92% at 3 months – 70% at 12 months – 80% at 24 months • failures not associated with calculi • no symptom outcome measure • Weidner et al,Drugs 58:103, 1999 Adjuvants to Antibiotics in Category II Prostatitis • Combination with alpha blockers – Barbalias GA et al J Urol 1998; 159 (3): 883. • Combination with prostatic massage – Shoskes DA, Zeitlin SI. Prostate Cancer and Prostate Diseases 1999; 2 (3): 159 • Long term-low dose suppressive therapy Quinolones: New vs Old • moxifloxacin (Avelox), gatifloxacin (Tequin) • superior for: – – – – Gram positive enterococcus anaerobes possibly chlamydia, mycoplasma • ciprofloxacin (Cipro), ofloxacin (Floxin) • superior for: - E. coli - Proteus - Pseudomonas Antibiotics for CPPS • Most common therapy for chronic prostatitis despite no randomized, placebo controlled studies • Belief that all prostatitis is due to infection – difficult to culture bacteria – biofilm 16S rRNA in CPPS • Krieger (1996) - signal seen in 77% of biopsies from men with CPPS • Keay (1999) - signal seen in 88% of biopsies from men with CaP • Hochreiter (2000) - 0/28 cadaveric organ donors had bacterial signal • Tanner (1999) - signal seen in 65% of EPS samples from men with CPPS – Predominance of Corynebacterial forms including newly discovered bacteria Role of Antibiotics in CP/CPPS • Multicenter study of 102 patients with prostatitis (II, IIIa and IIIb) • Recent UTI excluded • 12 weeks of ofloxacin • regardless of category, 57% felt moderate to marked improvement • no difference in response by category, antibody status or WBC count • No help if no improvement by 4 weeks Why Might Antibiotics Help CPPS? • All prostatitis is bacterial – why most patients fail? – why no improvement after RP – why immunosuppression helps? • Antibiotics have direct anti-inflammatory effects – quinolones, macrolides and tetracyclines block IL-6 and IL-8 • Intracellular pathogens not detected – chlamydia, E. coli • Placebo effect Conclusions • Antibiotics have definite role for category II chronic prostatitis • Many patients with category III will respond but mechanism unclear • Compelling evidence that some with nonuropathogens have infection but many don't • Bacteriologic cure not equivalent to cure • Prospective randomized placebo controlled trial should help settle in 2002 CCF Diagnostic Protocol • Off antibiotics for at least 2 weeks • History, Physical, NIH-CPSI • Uroflow, ultrasound bladder residual • Urethral swab, EPS +/- semen • Bacterial cultures for 5 days • Post ejaculatory pain or recurrent category II -> TRUS • Cysto for hematuria or suspected stricture • Hydrodistension if suspect IC CCF Treatment Protocol • Category II – antibiotics +/- massage +/- tamsulosin • Category III – antibiotics +/- massage – antifungal if hyphae or prolonged Ab – tamsulosin for voiding symptoms – Prosta-Q 2-3x per day for 1 month – empiric Proscar or Elmiron – physiotherapy, Elavil, Neurontin, Zanaflex