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 non- uropathogens 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