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Diagnosis and treatment of prostatic infections
DIAGNOSIS AND TREATMENT OF PROSTATIC INFECTIONS A N T H O N Y J. S C H A E F F E R , M.D. F r o m the D e p a r t m e n t of Urology, Northwesterrf University Medical School, Chicago, Illinois
~ o s t a t i t i s is one of the most common inflammatory eases encountered in urologic practice on the part ~ : both patient and physician. The diagnosis re!~ires careful attention to details and much panee. New antimierobials have improved therapy ~ d hold promise for better results in the future.
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Definition and Classification " e prostatitis, the degree of inflammatory at can be found in normal prostatic fluid be determined. This is done by micronination of expressed prostatic fluid and ~e number of white blood cells per high1. Available data suggest that white blood rely present in normal prostatic fluid. We 9 consecutive patients with no history, or physical findings (excluding prostatic ~ l u i d evaluation) of urinary tract inflammation, ~mal prostate glands by digital examination, and ~:~wer than 2 white blood cells per high-power field ~i~ the first 10 mL of voided urine and no or insignifiC a n t growth on urine cultural (Fig. 1). Of these pa~eflts, 31 were judged to have no urologic disease ~ n d they had prostatic fluid containing 0 7 -+ 0 41 ~ h i t e blood cells per high-power field (mean +_ ~i~ndard error of mean), and 88 with a vat:cry of ~i0ninflammatory urologic diseases had 3.8 _ 0.83 hite blood cells per high-power field in the pros~!~fic fluid. There were 2 white blood cells or more ~ high-power field observed in 97 percent of the @~iatients with no urologic disease and in 75 percent vith noninflammatory urologic disease and normal ~0state glands by digital examination. Only 13 of m 119 patients in these two groups had 10 white lood cells or more per high-power field. Similar re~ts have been reported by Blacklock2 and Ander~on and Weller.3 It appears therefore that clinically ignifieant inflammation is present when prostatic i~id contains 10 or more white blood cells per high~wer field. The distinguishing characteristics of
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FIGURE l. Number of white blood cells per highpower microscopic field in prostatic fluid from patients with no urologic disease or noninflammatory urologic disease. patients with bacterial or nonbacterial prostatitis are summarized in Table I. All patients with bacterial or nonbaeterial prostatitis have evidence of inflammation in their expressed prostatic secretions, and therefore they cannot be distinguished by the number of inflammatory cells. Patients with bacterial prostatitis, both acute and chronic, are distinguished from those with nonbacterial prostatitis based on mierobiologie parameters of the urinary tract and prostatic secretions. In virtually all patients with bacterial prostatitis, urinary tract infections occur and prostatic secretions contain bacteria. Conversely, patients with nonbaeterial prostatitis have no urinary tract infections and no bacterial growth in cultures of the prostatie secretions. Patients with pain in the prostate (prostatodynia) may have complaints of urinary
~$UPPLEMENTTO UROLOGY / NOVEMBER1990 / VOLUMEXXXVI, NUMBER5
13
TABLE I.
Prostatodynia*
Classification o] prostatitis
Evidence of Inflammation (EPS)
Culture (EPS)
Positive (Bladder)
Common Etiologic Bacteria
Exi
Acute bacterial + + + +~ Enterobacteriaceae prostatitis Chronic bacterial + + + +$ Enterobaeteriaceae prostatitis "Nonbacterial" + + 0 0 ? prostatitis Pelviperineal + 0 0 0 0 pain KEY:EPS = expressedprostatic secretion. *Pain in prostate. ~Aeute bacterial prostatitis nearly always accompaniedby bladder infection. $Characterized by recurrent bacterinria, at varying intervals up to several months, after stopping antimierobial therapy. urgency, dysuria, poor urine flow, or prostatic discomfort but no significant inflammation or bacteria in the prostatic fluid. Many patients are probably unable to differentiate prostatic pain from pelvic or perineal symptoms, and pelviperineal pain is therefore a more appropriate term to describe this condition.
Segmental bacteriologic localization cultures Bacterial prostatitis can be differentiated from nonbacterial prostatitis only by sequential, quantitative bacteriologic cultures of the urethra, bladder urine, and prostatic secretions. W h e n the patient has an infection, all specimens will show bacterial growth. In such cases the patient should be treated with an antimicrobial drug such as nitrofurantoin that will sterilize the bladder urine and clear the urethra of prostatic organisms without altering the prostatic microbial flora. Demonstration of bacteria in the post-prostatic massage urine or expressed prostatic secretions when the urethra and midstream urine specimens show no growth is highly diagnostic of bacterial prostatitis. Alternatively, a significant increase of a log or more in the bacterial count in the prostatic specimens w h e n c o m p a r e d w i t h the urethral specimen is considered diagnostic of bacterial prostatitis.
Bacterial prostatitis Bacterial prostatitis is caused by the same organisms responsible for urinary tract infections: Escherichia coli and other members of Enterobacteriaceae family predominate; Pseudomonas and Enterococcus (Streptococcus faecalis) are less common. Mixed infections involving two or more strains or classes of microorganisms are not uncommon. The pathogenesis of bacterial prostatitis is unknown. Presumably ascending urethral infection after a vaginal or rectal inoculation of the urinary meatus during sexual intercourse plays an important
role. Direct extension, or lymphogenons spread fecal microorganisms as well as hematogen: spread are also possible routes of infection. Sorni~ vestigators have postulated that reflux of urine !i the prostatic ducts can cause prostatic calculi cause the stones contain constituents commo found in urine but foreign to prostatic secreti~ These stones are very prevalent in men over the: of fifty and usually produce no symptoms. How~! if bacteria become entrapped within the stones; ~ may act as a nidus for bacteria, protecting t~ from the action of the antimicrobial drugs. 4
Acute bacterial prostatitis Acute bacterial prostatitis is usually dramati~ presentation and easy to diagnose on physical amination. The disease is associated with large ni bers of bacteria in the prostatic secretions an¢ bladder urine and is curable with antimicr~! therapy. It is characterized by malaise, fever, li back or perineal pain, and myalgia for several d prior to onset of symptoms of urinary frequel dysuria, and bladder outlet obstruction. Palpal of the prostate reveals a hard, tender, irre~ gland that is w a r m to the touch. Patients with a~ bacterial prostatitis respond dramatically to anti crobial drugs that do not normally achieve th:! peutic levels in the prostatic fluid. If the patie~ very toxic, he is hospitalized and treated with biotics, typically an aminoglycoside-penicillin Ci bination. Supportive measures such as analg~ antipyretics, hydration, bedrest, and stool sore! should be instituted. If a patient cannot void, sui pubic needle aspiration or catheter placement rat than urethral catheterization is recommended the patient is treated as an outpatient, trimet prim-sulfamethoxazole or a fluoroquinolone, s as ciprofloxaein or norfloxaein, can be prescri] and should be continued for at least fourteen thirty days.
SUPPLEMENT TO UROLOGY / NOVEMBER1090 / VOLUMEXXXVI,
's a potential but rare complication of rial prostatitis. If the gland is fluetuant n, perineal or transurethral drainage ~rformed as soon as possible. Granulomatitis is a histologie stage of resolving rial prostatitis that is usually detected as of prostatic induration suspicious of earthe prostate gland is hard, particularly [ months of therapy, the possibility of underlying malignancy should be considered. The posity of tuberculosis or a rare mycotic infection of ~ e p r o s t a t e should be considered in the differential
~osis.
~hronic bacterial prostatitis ~ C h r o n i c bacterial prostatitis is a subtle disease racterlzed by relatively asymptomatic periods ~een episodes of recurrent bacteriuria. It is im~hssible to diagnose by physical examination, is ~used by small numbers of bacteria in the prostatic l~id, and is very difficult to eradicate with antimi~obial therapy. Most patients are asymptomatic un~[!! they have recurrent urinary tract infections, a ~ l m a r k of this condition. Bacterial lower urinary et localization studies are a prerequisite for anti]erobial therapy.
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Management ~ Trimethoprim-sulfamethoxazole (160 mg/800 mg ~ i e e a day for 12 weeks) will cure about 30-40 per~ n t of patients. Continued therapy rarely will hieve additional cures. If the organism is resistant ~'itrimethoprim or if it persists in cultures of pros~tie secretions obtained during the first few weeks : therapy, further treatment with trimethoprim!famethoxazole is pointless. Failure of trimethoim-sulfamethoxazole therapy is usually not due to ~velopment of bacterial resistance to trimethoira, but rather to persistence of baeteria within the !~ora amylacea or prostatic calculi within the ~ t a t e . Success in treating chronic bacterial pros~titis also has been reported with carbenicillin inlanyl sodium, ervthrom cin, and minoc cline ~ g e of the patients treate~ with carbenicilli~ were ~!iQwed for more than one month. Since relapse afi ~ a month is common after an apparently successi~~ eatment of ehronic bacterial prostatitis, further ~ i e s are warranted to substantiate the efficacy of ~ese drugs Occasionally, patients who are not i i~rgd by these agents may benefit from a two to ~fir'week course of kanamycin. aoroquinolones, ciprofloxacin and norflox'e been studied in the treatment of chronic prostatitis. The fluoroquinolones have a ectrum of activity against aerobic gram_
negative and gram-positive bacteria. 5-7 Their low protein binding, small molecular size, high lipid solubility, and pKa values between 6 and 9 appear to favor their penetration into, and e n t r a p m e n t within, the prostate with tissue concentrations of 1.5-3 /zg/g of prostate tissue. These prostate levels are up to twofold higher than peak serum concentrations and are significantly higher than the minimum inhibitory concentrations of most uropathogens. 8,9 Initial studies have shown that norfloxacin and ciprofloxacin have achieved 60-92 percent cure rates in the treatment of chronic bacterial prostatitis. 10-12The high cure rates (74-92 %) were achieved in patients followed up for 1 to 2.5 months. Thus recent studies ls,14 utilizing ciprofloxacin and norfloxacin reported twelve- and six-month followups and cure rates of 53-64 percent, respectively. Weidner, Schiefer, and Dalhoffi ~ treated 17 men (age 20-53 years; mean 38 years) with chronic bacterial prostatitis (duration of symptoms more than 1 year). All had been treated previously with trimethoprim and/or trimethoprim-sulfamethoxazole for at least six weeks without showing improvement. Patients received 500 mg of eiprofloxacin orally twice daily for two weeks. Of 12 patients with E. coli prostatitis, treatment with ciprofloxacin was completed according to the protocol in 10, 1 patient did not reach a twelvemonth follow-up, and 1 patient stopped therapy because of severe headaches. No patients had signs of bacterial infection in a specimen during therapy. Thus, of the 10 patients with E. coli prostatitis and twelve-month follow-up, E. coli was eradicated in 5. Two patients had low numbers of E. coli on follow-up cultures but, on subsequent examinations, signs of E. coli infection could not be confirmed. The drug failed in 3 men, and in all 3 cases the reisolated E. coli strains were susceptible to ciprofloxacin. One patient stopped therapy because of severe side effects. Five patients had prostatitis due to other microorganisms. All patients completed the one-year follow-up. The causative agents were Enterococcus faeealis (3 patients), Pseudomonas aeruginosa (1 patient), and Enterobacter (1 patient). Of these patients, the Enterobacter prostatitis was cured but ciprofloxacin treatment was not effective in patients with E. faecalis and P. aeruginosa prostatitis. Thus, 8 of 15 patients (53 % ) with twelve-month follow-up were cured. Schaeffer assessed effieacy of norfloxacin in the treatment of ehronic baeterial prostatitis in 15 men (age 30-74 years; mean 61 years). All patients had bacterial prostatitis refractory to trimethoprim-sulfamethoxazole and/or earbenicillin. They were
~PLEMENT TO UROLOGY / NOVEMBER1990 / VOLUMEXXXVI, NUMBER5
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treated with 400 mg twice a day for twenty-eight days. All the pathogens were sensitive to norfloxacin and absent in prostatic fluid cultures obtained during therapy. One patient had negative posttherapy prostatic fluid cultures but was lost to follow-up at one month. Of the 14 patients followed for at least six months, 9 (64 %) were cured of the' original infection. Six of these remained uninfected and had negative prostatic secretion urine cultures at least six months and were uninfected at two years' follow-up. In 3 patients, the urinary tract infections recurred with new pathogens after post-therapy negative prostatic fluid cultures. Bacterial prostatitis with the original pathogen recurred in 5 patients within two months of completing therapy. The bacteria remained susceptible to norfloxacin but could not be eradicated with thirty to ninety days of additional norfloxacin therapy. Cures were achieved in 9 of 12 patients with E. coli and none of 2 with Pseudomonas prostatitis. No patients experienced significant adverse effects. Overall these data suggest that both ciprofloxacin or norfloxacin are effective and safe for treatment of chronic refractory bacterial prostatitis. Patients who fail antimicrobial therapy may be given low-dose suppressive antimicrobial drugs such as trimethoprim-sulfamethoxazole, nitrofurantoin, or tetracycline. It should be emphasized that discontinuation of therapy will eventually result in recurrent bacteriuria. Transurethral resection of the prostate is the only alternative short of radical prostatectomy for surgical management of bacterial prostatitis. Transurethral prostateetomy is curative only if all the foci of infected tissue and calculi are removed. Since most inflammation of chronic prostatitis occurs in the periphery of the gland, ~s and all the duets from the peripheral zone empty into the urethra distal to the verumontanum, ~ radical transurethral resection distal to the verumontanum is required to remove the infected tissue, and this procedure carries a high risk of urinary incontinence. About one third of patients with well-documented bacterial prostatitis have been cured by this technique) v
Nonbacterial prostatitis Nonbaeterial prostatitis is approximately eight times more common than bacterial prostatitis. The patient with nonbaeterial prostatitis is characterized by irritative or obstructive voiding symptoms or pain localized to the pelvis, perineal, serotal, or lowback area. However, approximately one third of the patients with nonbaeterial prostatitis are asymptomarie. Since the etiology is unknown, treatment is empiric and often unrewarding. If Chlamydia or
16
Ureaplasma are a likely cause of urethritis associated: with nonbacterial prostatitis, a clinical trial of tetra~ eycline for seven days is reasonable. The empiric ad, ministration of other antimicrobial drugs is inappro: priate and ineffective. Management should include. a frank discussion about the unknown, p r o b a b l y noninfectious etiology of the condition and efforts to: relieve symptoms. Most acute Symptoms b e n e f i t from hot sitz-baths and short-term use of a n t i - i n flammatory drugs (e.g., ibuprofen, 600 mg orall}i~ q.i.d.). Irritative voiding dysfunction usually rei~ sponds to the use of anticholinergics, for example:if oxybutynin chloride, 5 mg orally t.i.d.
Pelviperineal pain (prostatodynia) Although some individuals may have symptoms ofiil prostatic origin, musculoskeletal abnormalities ar~!ii probably responsible for much of the symptomatoi~!i ogy. For example, patients with pelvic symptoms~!! and a poor urinary stream may have detrus0~ii sphincter dyssynergia that is responsive to therap~ i with phenyoxybenzamine, 10 mg orally at bedtim~jil or b.i.d.; or prazosin, 1 or 2 mg orally b.i.d. Th~i dosage must be titrated to individual tolerance t0~ minimize side effects. Summary The diagnosis and management of ] pelviperineal pain is a challenge to Careful examination of the prostatic t teriologie cultures to differentiate b nonbaeterial prostatitis are essential. therapy is effective in the majority acute or chronic bacterial prostatitis. prostatitis is the most common type The etiology is unknown and treatr peated antimierobial therapy is ineffi blocking agents may relieve symptom. perineal pain may be of prostatic orJ nonprostatic causes should be sought. 303 East Chicago Chicago, Illino References 1. SehaefferAJ, et ah Prevalence and significanceof inflammation, ] Urol 125:215-219 (1981). 2. BlacldockNJ: Someobservationson prostatitis, in Willi~!i~~ DC, BriggsMH, and Stanford M (Eds): Advancesin the Stud~[~ the Prostate London William Heinemann Medical BooksLt'di~ 1969, pp 37-55. : ~! 3. Anderson RU, and Weller C: Prostatic secretion leuko~ t~i studies in non-bacterial prostatitis (prostatosis) J Urol 121: ~i 294 (1979). 4. MearesEM Jr: Infectionstonesof the prostate gland, la, ratory diagnosis and clinical management Urology4: 560e, (197. 4)'ehaeffer AJ: Multielinic study of norfloxacin for treat~~ of urinary tract infections, Am J Med 82 (Suppl. 6B): 531'
SUPPLEMENTTO UROLOGY / NOVEMBER1990 / VOLUMEXXXVI, NUMBr~'~:~
iW ~'q'abbaj J, Hoagland VL, and Shih WJ: Multiclinic compara~* ~.~,, of norfloxacin and trimethoprim-sulfamethoxazole for ~isrntu:~ of urinary tract infections, Antimicrob Agents Che~ e i 27:297-301 (1985). ~ ~ Downs J,' Andriole VT and Ryan JL: In vitro activity of ~(0366 against ehnmal urinary pathogens including gentaml~resiStant Pseudomonas aeruginosa, Antimicrob Agents Cher 21:670-672 (1982). ~-Hoo!oer DC, and Wolfson JS: The fluoroquinolones: phar-clinieal uses, and toxicities in humans, Antimicrob ~n~s Chemother 28:716-721 (1985). ~ !gBl ~er' eron MG, et al: Norfloxacin penetration into human ~ and prostatic tissues, Antimicrob Agents Chemother 28: '~350 (1985). ~ j , Sabbaj J, Hoagland VL, and Cook T: Norfloxacin versus ~;i~noxazolc in the treatment of recurring urinary tract infec~ in men, Stand J Infect Dis 48: (Suppl.) 48-53 (1986). .
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11. Bologna M, e t a h Norfloxacin in prostatitis: correlation between HPLC tissue concentrations and clinical results, Drugs Exp Clin lqes 11:95-100 (1985). 12. Chflds SJ: Treatment of chronic bacterial prostatitis with ciprofloxacin, Infect Surg 6:649 (1987). 13. Weidner W, Schiefer HG, and Dalhoff A: Treatment of chronic bacterial prostatitis with ciprofloxacin, results of a oneyear follow-up study, Am J Med 82: (Suppl. 4A): 280-283 (1987). 14. Schaeffer AJ, and Darras FS: The efficacy of norfloxacin in the treatment of chronic bacterial prostatitis refractory to trimethoprirn-sulfamethoxazole and/or carbenieillin, J Urol (in press). 15. McNeal JE: Regional morphology and pathology of the prostate, Am J Clin Pathol 49:347-357 (1968). 16. Blacklock NJ: Anatomical factors in prostatitis, Br J Urol 46:47-54 (1974). 17. Meares EM Jr: Prostatitis syndromes', new perspectives about old woes, J Urol 123:141-147 (1980).
VOLUME XXXVI, NUMBER 5
17
~ o s t a t i t i s is one of the most common inflammatory eases encountered in urologic practice on the part ~ : both patient and physician. The diagnosis re!~ires careful attention to details and much panee. New antimierobials have improved therapy ~ d hold promise for better results in the future.
4055-
~
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W~
"o
Definition and Classification " e prostatitis, the degree of inflammatory at can be found in normal prostatic fluid be determined. This is done by micronination of expressed prostatic fluid and ~e number of white blood cells per high1. Available data suggest that white blood rely present in normal prostatic fluid. We 9 consecutive patients with no history, or physical findings (excluding prostatic ~ l u i d evaluation) of urinary tract inflammation, ~mal prostate glands by digital examination, and ~:~wer than 2 white blood cells per high-power field ~i~ the first 10 mL of voided urine and no or insignifiC a n t growth on urine cultural (Fig. 1). Of these pa~eflts, 31 were judged to have no urologic disease ~ n d they had prostatic fluid containing 0 7 -+ 0 41 ~ h i t e blood cells per high-power field (mean +_ ~i~ndard error of mean), and 88 with a vat:cry of ~i0ninflammatory urologic diseases had 3.8 _ 0.83 hite blood cells per high-power field in the pros~!~fic fluid. There were 2 white blood cells or more ~ high-power field observed in 97 percent of the @~iatients with no urologic disease and in 75 percent vith noninflammatory urologic disease and normal ~0state glands by digital examination. Only 13 of m 119 patients in these two groups had 10 white lood cells or more per high-power field. Similar re~ts have been reported by Blacklock2 and Ander~on and Weller.3 It appears therefore that clinically ignifieant inflammation is present when prostatic i~id contains 10 or more white blood cells per high~wer field. The distinguishing characteristics of
~JC.) ",~- (]3
"
~y
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1918" 171615" 141312Il-
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N o U r o l o g i c Disease
Non-inflammatory
Urologic Disease
FIGURE l. Number of white blood cells per highpower microscopic field in prostatic fluid from patients with no urologic disease or noninflammatory urologic disease. patients with bacterial or nonbacterial prostatitis are summarized in Table I. All patients with bacterial or nonbaeterial prostatitis have evidence of inflammation in their expressed prostatic secretions, and therefore they cannot be distinguished by the number of inflammatory cells. Patients with bacterial prostatitis, both acute and chronic, are distinguished from those with nonbacterial prostatitis based on mierobiologie parameters of the urinary tract and prostatic secretions. In virtually all patients with bacterial prostatitis, urinary tract infections occur and prostatic secretions contain bacteria. Conversely, patients with nonbaeterial prostatitis have no urinary tract infections and no bacterial growth in cultures of the prostatie secretions. Patients with pain in the prostate (prostatodynia) may have complaints of urinary
~$UPPLEMENTTO UROLOGY / NOVEMBER1990 / VOLUMEXXXVI, NUMBER5
13
TABLE I.
Prostatodynia*
Classification o] prostatitis
Evidence of Inflammation (EPS)
Culture (EPS)
Positive (Bladder)
Common Etiologic Bacteria
Exi
Acute bacterial + + + +~ Enterobacteriaceae prostatitis Chronic bacterial + + + +$ Enterobaeteriaceae prostatitis "Nonbacterial" + + 0 0 ? prostatitis Pelviperineal + 0 0 0 0 pain KEY:EPS = expressedprostatic secretion. *Pain in prostate. ~Aeute bacterial prostatitis nearly always accompaniedby bladder infection. $Characterized by recurrent bacterinria, at varying intervals up to several months, after stopping antimierobial therapy. urgency, dysuria, poor urine flow, or prostatic discomfort but no significant inflammation or bacteria in the prostatic fluid. Many patients are probably unable to differentiate prostatic pain from pelvic or perineal symptoms, and pelviperineal pain is therefore a more appropriate term to describe this condition.
Segmental bacteriologic localization cultures Bacterial prostatitis can be differentiated from nonbacterial prostatitis only by sequential, quantitative bacteriologic cultures of the urethra, bladder urine, and prostatic secretions. W h e n the patient has an infection, all specimens will show bacterial growth. In such cases the patient should be treated with an antimicrobial drug such as nitrofurantoin that will sterilize the bladder urine and clear the urethra of prostatic organisms without altering the prostatic microbial flora. Demonstration of bacteria in the post-prostatic massage urine or expressed prostatic secretions when the urethra and midstream urine specimens show no growth is highly diagnostic of bacterial prostatitis. Alternatively, a significant increase of a log or more in the bacterial count in the prostatic specimens w h e n c o m p a r e d w i t h the urethral specimen is considered diagnostic of bacterial prostatitis.
Bacterial prostatitis Bacterial prostatitis is caused by the same organisms responsible for urinary tract infections: Escherichia coli and other members of Enterobacteriaceae family predominate; Pseudomonas and Enterococcus (Streptococcus faecalis) are less common. Mixed infections involving two or more strains or classes of microorganisms are not uncommon. The pathogenesis of bacterial prostatitis is unknown. Presumably ascending urethral infection after a vaginal or rectal inoculation of the urinary meatus during sexual intercourse plays an important
role. Direct extension, or lymphogenons spread fecal microorganisms as well as hematogen: spread are also possible routes of infection. Sorni~ vestigators have postulated that reflux of urine !i the prostatic ducts can cause prostatic calculi cause the stones contain constituents commo found in urine but foreign to prostatic secreti~ These stones are very prevalent in men over the: of fifty and usually produce no symptoms. How~! if bacteria become entrapped within the stones; ~ may act as a nidus for bacteria, protecting t~ from the action of the antimicrobial drugs. 4
Acute bacterial prostatitis Acute bacterial prostatitis is usually dramati~ presentation and easy to diagnose on physical amination. The disease is associated with large ni bers of bacteria in the prostatic secretions an¢ bladder urine and is curable with antimicr~! therapy. It is characterized by malaise, fever, li back or perineal pain, and myalgia for several d prior to onset of symptoms of urinary frequel dysuria, and bladder outlet obstruction. Palpal of the prostate reveals a hard, tender, irre~ gland that is w a r m to the touch. Patients with a~ bacterial prostatitis respond dramatically to anti crobial drugs that do not normally achieve th:! peutic levels in the prostatic fluid. If the patie~ very toxic, he is hospitalized and treated with biotics, typically an aminoglycoside-penicillin Ci bination. Supportive measures such as analg~ antipyretics, hydration, bedrest, and stool sore! should be instituted. If a patient cannot void, sui pubic needle aspiration or catheter placement rat than urethral catheterization is recommended the patient is treated as an outpatient, trimet prim-sulfamethoxazole or a fluoroquinolone, s as ciprofloxaein or norfloxaein, can be prescri] and should be continued for at least fourteen thirty days.
SUPPLEMENT TO UROLOGY / NOVEMBER1090 / VOLUMEXXXVI,
's a potential but rare complication of rial prostatitis. If the gland is fluetuant n, perineal or transurethral drainage ~rformed as soon as possible. Granulomatitis is a histologie stage of resolving rial prostatitis that is usually detected as of prostatic induration suspicious of earthe prostate gland is hard, particularly [ months of therapy, the possibility of underlying malignancy should be considered. The posity of tuberculosis or a rare mycotic infection of ~ e p r o s t a t e should be considered in the differential
~osis.
~hronic bacterial prostatitis ~ C h r o n i c bacterial prostatitis is a subtle disease racterlzed by relatively asymptomatic periods ~een episodes of recurrent bacteriuria. It is im~hssible to diagnose by physical examination, is ~used by small numbers of bacteria in the prostatic l~id, and is very difficult to eradicate with antimi~obial therapy. Most patients are asymptomatic un~[!! they have recurrent urinary tract infections, a ~ l m a r k of this condition. Bacterial lower urinary et localization studies are a prerequisite for anti]erobial therapy.
~a
~
Management ~ Trimethoprim-sulfamethoxazole (160 mg/800 mg ~ i e e a day for 12 weeks) will cure about 30-40 per~ n t of patients. Continued therapy rarely will hieve additional cures. If the organism is resistant ~'itrimethoprim or if it persists in cultures of pros~tie secretions obtained during the first few weeks : therapy, further treatment with trimethoprim!famethoxazole is pointless. Failure of trimethoim-sulfamethoxazole therapy is usually not due to ~velopment of bacterial resistance to trimethoira, but rather to persistence of baeteria within the !~ora amylacea or prostatic calculi within the ~ t a t e . Success in treating chronic bacterial pros~titis also has been reported with carbenicillin inlanyl sodium, ervthrom cin, and minoc cline ~ g e of the patients treate~ with carbenicilli~ were ~!iQwed for more than one month. Since relapse afi ~ a month is common after an apparently successi~~ eatment of ehronic bacterial prostatitis, further ~ i e s are warranted to substantiate the efficacy of ~ese drugs Occasionally, patients who are not i i~rgd by these agents may benefit from a two to ~fir'week course of kanamycin. aoroquinolones, ciprofloxacin and norflox'e been studied in the treatment of chronic prostatitis. The fluoroquinolones have a ectrum of activity against aerobic gram_
negative and gram-positive bacteria. 5-7 Their low protein binding, small molecular size, high lipid solubility, and pKa values between 6 and 9 appear to favor their penetration into, and e n t r a p m e n t within, the prostate with tissue concentrations of 1.5-3 /zg/g of prostate tissue. These prostate levels are up to twofold higher than peak serum concentrations and are significantly higher than the minimum inhibitory concentrations of most uropathogens. 8,9 Initial studies have shown that norfloxacin and ciprofloxacin have achieved 60-92 percent cure rates in the treatment of chronic bacterial prostatitis. 10-12The high cure rates (74-92 %) were achieved in patients followed up for 1 to 2.5 months. Thus recent studies ls,14 utilizing ciprofloxacin and norfloxacin reported twelve- and six-month followups and cure rates of 53-64 percent, respectively. Weidner, Schiefer, and Dalhoffi ~ treated 17 men (age 20-53 years; mean 38 years) with chronic bacterial prostatitis (duration of symptoms more than 1 year). All had been treated previously with trimethoprim and/or trimethoprim-sulfamethoxazole for at least six weeks without showing improvement. Patients received 500 mg of eiprofloxacin orally twice daily for two weeks. Of 12 patients with E. coli prostatitis, treatment with ciprofloxacin was completed according to the protocol in 10, 1 patient did not reach a twelvemonth follow-up, and 1 patient stopped therapy because of severe headaches. No patients had signs of bacterial infection in a specimen during therapy. Thus, of the 10 patients with E. coli prostatitis and twelve-month follow-up, E. coli was eradicated in 5. Two patients had low numbers of E. coli on follow-up cultures but, on subsequent examinations, signs of E. coli infection could not be confirmed. The drug failed in 3 men, and in all 3 cases the reisolated E. coli strains were susceptible to ciprofloxacin. One patient stopped therapy because of severe side effects. Five patients had prostatitis due to other microorganisms. All patients completed the one-year follow-up. The causative agents were Enterococcus faeealis (3 patients), Pseudomonas aeruginosa (1 patient), and Enterobacter (1 patient). Of these patients, the Enterobacter prostatitis was cured but ciprofloxacin treatment was not effective in patients with E. faecalis and P. aeruginosa prostatitis. Thus, 8 of 15 patients (53 % ) with twelve-month follow-up were cured. Schaeffer assessed effieacy of norfloxacin in the treatment of ehronic baeterial prostatitis in 15 men (age 30-74 years; mean 61 years). All patients had bacterial prostatitis refractory to trimethoprim-sulfamethoxazole and/or earbenicillin. They were
~PLEMENT TO UROLOGY / NOVEMBER1990 / VOLUMEXXXVI, NUMBER5
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treated with 400 mg twice a day for twenty-eight days. All the pathogens were sensitive to norfloxacin and absent in prostatic fluid cultures obtained during therapy. One patient had negative posttherapy prostatic fluid cultures but was lost to follow-up at one month. Of the 14 patients followed for at least six months, 9 (64 %) were cured of the' original infection. Six of these remained uninfected and had negative prostatic secretion urine cultures at least six months and were uninfected at two years' follow-up. In 3 patients, the urinary tract infections recurred with new pathogens after post-therapy negative prostatic fluid cultures. Bacterial prostatitis with the original pathogen recurred in 5 patients within two months of completing therapy. The bacteria remained susceptible to norfloxacin but could not be eradicated with thirty to ninety days of additional norfloxacin therapy. Cures were achieved in 9 of 12 patients with E. coli and none of 2 with Pseudomonas prostatitis. No patients experienced significant adverse effects. Overall these data suggest that both ciprofloxacin or norfloxacin are effective and safe for treatment of chronic refractory bacterial prostatitis. Patients who fail antimicrobial therapy may be given low-dose suppressive antimicrobial drugs such as trimethoprim-sulfamethoxazole, nitrofurantoin, or tetracycline. It should be emphasized that discontinuation of therapy will eventually result in recurrent bacteriuria. Transurethral resection of the prostate is the only alternative short of radical prostatectomy for surgical management of bacterial prostatitis. Transurethral prostateetomy is curative only if all the foci of infected tissue and calculi are removed. Since most inflammation of chronic prostatitis occurs in the periphery of the gland, ~s and all the duets from the peripheral zone empty into the urethra distal to the verumontanum, ~ radical transurethral resection distal to the verumontanum is required to remove the infected tissue, and this procedure carries a high risk of urinary incontinence. About one third of patients with well-documented bacterial prostatitis have been cured by this technique) v
Nonbacterial prostatitis Nonbaeterial prostatitis is approximately eight times more common than bacterial prostatitis. The patient with nonbaeterial prostatitis is characterized by irritative or obstructive voiding symptoms or pain localized to the pelvis, perineal, serotal, or lowback area. However, approximately one third of the patients with nonbaeterial prostatitis are asymptomarie. Since the etiology is unknown, treatment is empiric and often unrewarding. If Chlamydia or
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Ureaplasma are a likely cause of urethritis associated: with nonbacterial prostatitis, a clinical trial of tetra~ eycline for seven days is reasonable. The empiric ad, ministration of other antimicrobial drugs is inappro: priate and ineffective. Management should include. a frank discussion about the unknown, p r o b a b l y noninfectious etiology of the condition and efforts to: relieve symptoms. Most acute Symptoms b e n e f i t from hot sitz-baths and short-term use of a n t i - i n flammatory drugs (e.g., ibuprofen, 600 mg orall}i~ q.i.d.). Irritative voiding dysfunction usually rei~ sponds to the use of anticholinergics, for example:if oxybutynin chloride, 5 mg orally t.i.d.
Pelviperineal pain (prostatodynia) Although some individuals may have symptoms ofiil prostatic origin, musculoskeletal abnormalities ar~!ii probably responsible for much of the symptomatoi~!i ogy. For example, patients with pelvic symptoms~!! and a poor urinary stream may have detrus0~ii sphincter dyssynergia that is responsive to therap~ i with phenyoxybenzamine, 10 mg orally at bedtim~jil or b.i.d.; or prazosin, 1 or 2 mg orally b.i.d. Th~i dosage must be titrated to individual tolerance t0~ minimize side effects. Summary The diagnosis and management of ] pelviperineal pain is a challenge to Careful examination of the prostatic t teriologie cultures to differentiate b nonbaeterial prostatitis are essential. therapy is effective in the majority acute or chronic bacterial prostatitis. prostatitis is the most common type The etiology is unknown and treatr peated antimierobial therapy is ineffi blocking agents may relieve symptom. perineal pain may be of prostatic orJ nonprostatic causes should be sought. 303 East Chicago Chicago, Illino References 1. SehaefferAJ, et ah Prevalence and significanceof inflammation, ] Urol 125:215-219 (1981). 2. BlacldockNJ: Someobservationson prostatitis, in Willi~!i~~ DC, BriggsMH, and Stanford M (Eds): Advancesin the Stud~[~ the Prostate London William Heinemann Medical BooksLt'di~ 1969, pp 37-55. : ~! 3. Anderson RU, and Weller C: Prostatic secretion leuko~ t~i studies in non-bacterial prostatitis (prostatosis) J Urol 121: ~i 294 (1979). 4. MearesEM Jr: Infectionstonesof the prostate gland, la, ratory diagnosis and clinical management Urology4: 560e, (197. 4)'ehaeffer AJ: Multielinic study of norfloxacin for treat~~ of urinary tract infections, Am J Med 82 (Suppl. 6B): 531'
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iW ~'q'abbaj J, Hoagland VL, and Shih WJ: Multiclinic compara~* ~.~,, of norfloxacin and trimethoprim-sulfamethoxazole for ~isrntu:~ of urinary tract infections, Antimicrob Agents Che~ e i 27:297-301 (1985). ~ ~ Downs J,' Andriole VT and Ryan JL: In vitro activity of ~(0366 against ehnmal urinary pathogens including gentaml~resiStant Pseudomonas aeruginosa, Antimicrob Agents Cher 21:670-672 (1982). ~-Hoo!oer DC, and Wolfson JS: The fluoroquinolones: phar-clinieal uses, and toxicities in humans, Antimicrob ~n~s Chemother 28:716-721 (1985). ~ !gBl ~er' eron MG, et al: Norfloxacin penetration into human ~ and prostatic tissues, Antimicrob Agents Chemother 28: '~350 (1985). ~ j , Sabbaj J, Hoagland VL, and Cook T: Norfloxacin versus ~;i~noxazolc in the treatment of recurring urinary tract infec~ in men, Stand J Infect Dis 48: (Suppl.) 48-53 (1986). .
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11. Bologna M, e t a h Norfloxacin in prostatitis: correlation between HPLC tissue concentrations and clinical results, Drugs Exp Clin lqes 11:95-100 (1985). 12. Chflds SJ: Treatment of chronic bacterial prostatitis with ciprofloxacin, Infect Surg 6:649 (1987). 13. Weidner W, Schiefer HG, and Dalhoff A: Treatment of chronic bacterial prostatitis with ciprofloxacin, results of a oneyear follow-up study, Am J Med 82: (Suppl. 4A): 280-283 (1987). 14. Schaeffer AJ, and Darras FS: The efficacy of norfloxacin in the treatment of chronic bacterial prostatitis refractory to trimethoprirn-sulfamethoxazole and/or carbenieillin, J Urol (in press). 15. McNeal JE: Regional morphology and pathology of the prostate, Am J Clin Pathol 49:347-357 (1968). 16. Blacklock NJ: Anatomical factors in prostatitis, Br J Urol 46:47-54 (1974). 17. Meares EM Jr: Prostatitis syndromes', new perspectives about old woes, J Urol 123:141-147 (1980).
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