Pii: s0090-4295(02)02300-2

Antimicrobial therapy is the standard of care for the unusual man with true chronic bacterial prostatitis but
does not have much of a role in the treatment of men with nonbacterial prostatitis. The fluoroquinolone
antibiotics given for 2 to 4 weeks will cure about 70% of chronic bacterial infections of the prostate. If this
treatment fails, the symptomatic manifestations of the infections can almost always be eliminated with
suppressive antimicrobial therapy using trimethoprim-sulfamethoxazole, a fluoroquinolone antibiotic, or
nitrofurantoin. UROLOGY 60 (Suppl 6A): 24–26, 2002. 2002, Elsevier Science Inc.
Antimicrobial therapy that is based upon the are ionized to varying degrees in biologic fluids.
results of bacteriologic investigation of the The degree of ionization is determined by both the urine and/or expressed prostatic secretions (EPS) dissociation constant (pKa) of the drug and the pH is the standard of care for men with chronic bacte- of the fluid. Agents with a pKa that approaches 7.4 rial prostatitis. Conversely, antimicrobial therapy (the pH of serum) are only partially charged in the has no proven impact on the symptoms or natural serum, whereas those with a pKa that differs sub- history of nonbacterial prostatitis, a disorder that is stantially from 7.4 are highly charged in the serum.
not believed to be caused by bacterial infection.
Trimethoprim and the fluoroquinolones are the only antimicrobial agents that have good activity BASIC PRINCIPLES OF ANTIMICROBIAL THERAPY
against gram-negative bacilli and that possess the Potentially Curative Therapy. Eradication of lo- pharmacologic characteristics that predict a capac- calized bacterial infections with antimicrobial ity for diffusion into the prostatic fluid. Clinical therapy requires sufficient levels of an appropriate experiences have demonstrated that these agents drug at the site of infection. Because infecting bac- are also the most effective for treatment of chronic teria are isolated from the prostatic fluid of men bacterial prostatitis. The optimal drug doses for with chronic bacterial prostatitis, it follows that the potentially curative therapy or for suppressive antimicrobial agent must achieve bactericidal lev- therapy are not well established, and the recom- els in this fluid. Although therapeutic levels of drug mendations that follow constitute the author’s ap- also must be achieved in the urine, this consider- proach rather than those recommended by the ation has limited clinical relevance because all manufacturer or cited in the Physicians Desk Refer- agents used for the treatment of chronic bacterial ence.2 Trimethoprim-sulfamethoxazole (160 and prostatitis are concentrated in the urine.
800 mg twice daily) over a 12-week period will A variety of pharmacologic properties determine cure about 40% of patients.3 It is probable that the whether a drug will diffuse into the prostatic fluid.1 sulfamethoxazole component of this combination To penetrate the prostatic epithelium, the agent agent has little therapeutic value, and that the effi- must be lipid soluble and have minimal binding to cacy of trimethoprim alone is similar to that of serum protein. In addition, ionized molecules do trimethoprim-sulfamethoxazole. The fluoroquino- not cross epithelial membranes. Most antimicro- lone antibiotics, such as ciprofloxacin (500 mg bial agents are either weak acids or weak bases and twice daily), given for 2 to 4 weeks cure about 70%of men with chronic bacterial prostatitis and will From the Division of Urology, University of Mississippi School of often cure men with persistent infection after treat- Medicine, Jackson, Mississippi, USA ment with trimethoprim-sulfamethoxazole.4–7 Reprint requests: Jackson E. Fowler, Jr, MD, University of Mis- Suppressive Therapy. Unlike conventional anti- sissippi Medical Center, Division of Urology, 2500 North StateStreet, Jackson, Mississippi 39216. E-mail: jfowler@surgery. microbial therapy, which is designed to eradicate the focus of infection in the prostate gland, and by 24 ALL RIGHTS RESERVED
definition, eliminate the cause of persistent bacte- tomatic episodes or if antimicrobial therapy did riuria, the goal of suppressive therapy is to reduce not lead to prompt symptomatic relief.
or eliminate bacterial growth in the urine only.
During the initial evaluation of men with symp- This usually results in complete symptomatic relief toms of chronic prostatitis, a second midstream and little risk of serious morbidity from infection bladder specimen (VB ) is obtained before or after a careful history and is examined microscopically Considerations important to drug selection for before physical examination. If the history does suppressive therapy differ substantially from those not suggest bacterial infection and there is no of conventional antimicrobial therapy. Agents pyuria, bacteriologic investigations of the urine or used for suppressive therapy must be well tolerated EPS are not warranted. Regardless of history, if during prolonged periods of administration and there is pyuria, the VB specimen is cultured. Fi- must be active against the infecting organism at nally, if the history is suggestive of bacterial infec- concentrations achievable in the urine. Most anti- tion and there is no pyuria, EPS is procured during biotics are physiologically concentrated in the examination of the prostate and cultured.
urine, achieving levels 50 to 100 times greater than Nitrofurantoin macrocrystals, 100 mg twice in serum. Because the susceptibility of most gram- daily for 7 days is recommended for the initial negative bacteria to an antimicrobial agent is di- treatment of suspected chronic bacterial prostati- rectly related to the concentration of the drug, it tis, and the patient is reevaluated 1 week after the follows that a variety of agents that are inappropri- first visit. Nitrofurantoin macrocrystals will not ate for the treatment of invasive infections may be eradicate bacteria in the prostate and will facilitate effective for suppressive therapy, and that antimi- the interpretation of subsequent lower tract bacte- crobial susceptibility testing may be critical for ap- rial localization studies.9 When pathogenic organ- isms are not isolated from the VB or EPS speci- Reported experiences with chronic bacterial pros- men, further antimicrobial therapy is not pursued tatitis indicate that low-dose trimethoprim (50 or 100 and the patient is considered to have nonbacterial mg once daily), trimethoprim-sulfamethoxazole (40 prostatitis. When gram-negative bacilli are isolated and 200 mg once daily), and nitrofurantoin (50 or from the VB or EPS specimen, the clinician may 100 mg once daily) are remarkably effective.1,8 A perform a lower tract bacterial localization study or large experience with these agents for prophylaxis simply treat the patient with a fluoroquinolone an- against frequent urinary tract reinfection in women tibiotic (such as ciprofloxacin, 500 mg, twice suggest that indefinite treatment is generally well tol- daily) for 3 weeks. Enterococcus infections should erated.1 Chronic low-dose fluoroquinolone antibi- be treated with ampicillin, 250 mg 4 times daily, otic therapy, such as ciprofloxacin (125 or 250 mg for 2 weeks. In the rare event that pathogenic or- once daily), is also well tolerated and may be more ganisms isolated from the VB or EPS specimen effective than the treatment regimens described appear resistant to a fluoroquinolone antibiotic, an above. However, the cost of the fluoroquinolones is alternative agent that exhibits activity should be substantially greater than that of generic tri- given at full oral dosage. If the isolate appears re- methoprim-sulfamethoxazole or nitrofurantoin. This sistant to all oral agents, it is reasonable to proceed issue may warrant careful consideration in an era of with fluoroquinolone antibiotic therapy.
cost containment in the healthcare system.
Surveillance cultures of the VB specimen at 4 and 12 weeks after treatment should be done todocument therapeutic efficacy. Men with persis- AN APPROACH TO THE DIAGNOSIS AND
tent bacteriuria should be retreated with a fluoro- TREATMENT OF CHRONIC BACTERIAL
quinolone antibiotic for 3 more weeks.
Chronic prostatic infections caused by organ- The symptoms of chronic bacterial prostatitis isms that are susceptible to the fluoroquinolone and of nonbacterial prostatitis are similar. How- antibiotics but that cannot be eradicated with 3 to 6 ever, the relative incidence of nonbacterial pros- weeks of treatment will rarely be cured with other tatitis is about 20 times greater than chronic bac- antimicrobial agents. Moreover, there is no con- terial prostatitis, and bacteriologic investigations vincing evidence that treatment with a fluoroquin- should be limited to patients with a high likelihood olone for longer than 6 weeks will increase the of bacterial infection. A history of culture-docu- likelihood of cure. For these reasons, the most log- mented bacteriuria, or of prompt symptomatic re- ical approach to subsequent treatment is suppres- sponses to prior antimicrobial therapy, or a urinal- sive antimicrobial therapy. Because this therapy is ysis suggesting bacteriuria, should raise concern associated with greater cost and potential morbid- about an infectious process. Conversely, the likeli- ity than conventional drug therapy, it is prudent to hood of chronic bacterial prostatitis is remote if clearly document prostatic infection with a lower past urine cultures have been sterile during symp- UROLOGY 60 (Supplement 6A), December 2002
chronic bacterial prostatitis with ciprofloxacin. Results of a 1. Stamey TA: Pathogenesis and Treatment of Urinary Tract one-year follow-up study. Am J Med 82: 280 –283, 1987.
Infections. Baltimore, Williams and Wilkins, 1980.
6. Schaeffer AJ, and Darras FS: The efficacy of norfloxacin 2. Physicians’ Desk Reference. Montvale, NJ, Medical Eco- in the treatment of chronic bacterial prostatitis refractory to trimethoprim-sulfamethoxazole and/or carbenicillin. J Urol 3. Schaeffer AJ, Chmiel JS, Grayhack JS: Natural history of 144: 690 –693, 1990.
prostatic inflammation. Abstract presented at of the Annual 7. Sabbaj J, Hoagland VL, and Cook T: Norfloxacin versus Meeting of the American Urological Association; 1985, 207A.
co-trimoxazole in the treatment of recurring urinary tract in- 4. Weidner W, Schiefer HG, and Brahler E: Refractory fections in men. Scand J Infect Dis Suppl 48: 48 –53, 1986.
8. Fowler JE Jr: Urinary Tract Infection and Urinary Inflam- chronic bacterial prostatitis: a re-evaluation of ciprofloxacin mation. Chicago, Year Book Medical Publisher, 1989.
treatment after a median followup of 30 months. J Urol 146:
9. Meares EM, and Stamey TA: Bacteriologic localization patterns in bacterial prostatitis and urethritis. Invest Urol 5:
5. Weidner W, Schiefer HG, and Dalhoff A: Treatment of DISCUSSION FOLLOWING DR. FOWLER’S PRESENTATION Anthony J. Schaeffer, MD (Chicago, Illinois): The recom-
sible pathogen. At the very least you should do a urine culture.
mendations we make for urinalysis and culture also serve to Is it mandatory to do a localization culture? That is the ques- rule out other conditions that the pelvic pain could be mask- ing or mimicking. Dr. Shoskes mentioned carcinoma in situ.
Dr. Schaeffer: Do we want to mandate a urine localization
You should do a urinalysis to rule out other conditions, and you ought to do a culture. If you have positive cultures, as Dr.
Michel Pontari, MD (Philadelphia, Pennsylvania): In
Fowler suggested, then you investigate localization, and if you terms of what we want to say about antibiotics, I know the have a positive urinalysis, you can start talking about other European Commission said in 1998 that all patients should have a course of antibiotics.1 Localization cultures or not, I Daniel A. Shoskes, MD (Weston, Florida): This is based on
think everybody deserves one 4- to 6-week course of antibiot- the supposition that you do not get symptoms from bacteria unless you have a urinary tract infection.
Dr. Schaeffer: We never see anybody like that. Approxi-
Dr. Schaeffer: Yes. That is true. Have you ever seen a person
mately 90% of our patients have already been treated.
with documented bacterial prostatitis, but without a urinary Dr. Nickel: The study I did was with primary care urolo-
gists, and those men treated with the quinolone are patients Dr. Shoskes: Because we are just commenting on particular
that this group does not usually see. I do not think we can case reports, I can think of several patients without a urinary make too many recommendations until we know the National tract infection who were found to have Escherichia coli; anti- Institutes of Health (NIH) RCT1 results. Right now, I still biotic treatment eradicated the E. coli and eradicated the recommend that every patient probably should have 1 trial of symptoms. This is a personal observation. Unless I have antibiotic. If it does not relieve symptoms, then it should not missed some of the published data, I do not think that it is J. Curtis Nickel, MD (Kingston, Ontario, Canada): We had
102 patients in our study; approximately 50% of them had a significant clinical improvement on fluoroquinolones without 1. Bjerklund Johansen TE, Gruneberg RN, Guibert J, et al: bacteria. So quinolones may do more than just treat bacterial The role of antibiotics in the treatment of chronic prostatitis: a infections. Or alternatively, we are not culturing the respon- consensus statement. Eur Urol 34: 457–466, 1998.
UROLOGY 60 (Supplement 6A), December 2002

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