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Intraprostatic Injection

In the early 2000s, the concept of injecting the prostate transperineally with a combination of steroids (betamethasone) and antibiotics (to prevent the steroid-induced local immunosuppression leading to abscess) gained currency through the efforts of European practitioners, and especially Dr Federico Guercini of Rome, Italy. Dr Guercini claims a high success rate (65% cured at 6 and 12 month follow-ups), and presented a paper on the treatment at the American Urological Association Meeting in 2002. Here is the abstract:

ULTRASOUND GUIDED INTRAPROSTATE INFILTRATION FOR CHRONIC PROSTATITIS-A MULTI-CENTRE STUDY

Federico Guercini*, Rome, Italy, Duke Bahn, Ventura,, CA, Cinzia Pajoncini, Rome, Italy, Luigi Mearini, Massimo Porena, Perugia, Italy

Introduction and Objectives:

Many therapeutic options are available for chronic prostatitis, none is completely efficacious. Systemic antibiotic therapy is useful, however the failure rate is high probably because of an associated local autoimmune disease process (with release of large quantities of TNF alfa), and the possible presence of so-called intraprostatic bacterial biofilms which the drugs cannot penetrate. Given this background we tested ultrasound guided intra-prostate infiltration of a cocktail of antibiotics and betamethazone, for a therapeutical option.

Methods:

150 patients, referred to us between 1999 and 2001 because of symptoms indicative of chronic prostatitis, were enrolled in this study. Before treatment, all patients was submitted to: 1) a clinical urological examination 2) TRUS with micturitional dynamics and uroflowmetry 3) routine cultures tests and DNA amplification with PCR of Chlamidia, Mycoplasmata, Gonorrhea and HPV. All tests were done on sperm and urine samples. During first consultation patients completed the NIH Prostatitis Symptoms Score (NIHPSS) and Prostatitis Symptoms Index (PSI) questionnaires. Patients were divided into three groups on the basis of laboratory results and each group received an antibiotic cocktail specifically designed against the infectious agents that had been detected, associated with betamethazone. Antibiotics were administered as prostate infiltration using the transperineal approach, guided by transrectal ultrasound. Administration was repeated after 7 and 14 days. Six and 12 months after the last infiltration patients were followed up with uroflowmetry, NIHPSS and PSI. Final assessment of the efficacy of therapy included not only the scores but also the patient's subjective judgement expressed as a "percentage overall improvement". The percentage judgements were arbitrarily divided into 4 classes: 0-30% - no improvement; 30-50% satisfactory improvement; 50-80% good improvement; 80-100% cured.

Results:

Data were analysed using the Wilcoxon test for paired data as follows: baseline vs 6 and 12 months. Statistical analysis of the results showed 65% of patients were included in the fourth group and 17% had obtained no improvement.

Conclusions:

We are of the opinion this is one of the more valid therapeutical approaches to chronic prostatitis. Results will undoubtedly improve once drugs such as anti-TNF alpha antibiodies are available to be injected into the prostate to inhibit the autoimmune disease process, which in this study was controlled with betametazone.


The controversial aspect of this treatment seems to involve its effectiveness and usefulness in cases of CP/CPPS rather than in cases of chronic bacterial prostatitis. In the latter, it seems about as effective as intramuscular injection of antibiotics, but, because of significant side-effects, is not widely used. However, when a steroid (or, in the future, other immunomodulant) is added, it may have some usefulness in chronic nonbacterial prostatitis too, since it allows strong immunosuppression/modulation to be delivered to the gland and not the entire body, thus avoiding the usual side-effects attendant on such treatment.

Dr. Guercini states that significant pain after infiltrations happens in patients treated with Clarithromycin (2-3% off all patients) for 10-15 minutes after infiltration. Hemospermia (blood in semen) happens in about 70% of patients, but, according to Dr Guercini, only in the first two ejaculations.

Dr. Gillenwater, who attended this lecture, noted that there were some studies 20-30 years ago showing that the availability of antibiotics in the prostate following the intraprostatic protocol is exactly the same as the amount you get when you give the patient an intramuscular shot of the same antibiotic. The success rate in his opinion was low and the complication rate was higher.

Expert opinion from Dr J. Curtis Nickel's "Textbook of Prostatitis":

Intraprostatic injection of antibiotics

Intraprostatic injection into the caudal prostate was possibly first described in 1983 by Baert et al. This was performed under "rectal control" for three patients with chronic bacterial prostatitis, diluting the following combination of antibiotics with lidocaine: amikacin, cefazolin, gentamicin, and thiamphenicol glycinate. The reason for including the report is that many urologists have anecdotally reported using intraprostatic injection of various antibiotics in chronic non-bacterial prostatitis, often with symptomatic relief lasting 3 months or so. Indeed, it is well-known to all urologists that prostatic biopsy is complicated, on some occasions, by life-threatening septicaemia especially with transrectal prostatic biopsy (unless preceded by colonic washouts and pre-biopsy gentamicin +/- a cephalosporin/quinolone by the intra-muscular route) (personal communication, K. Kaye). TRANSPERINEAL BIOPSY AS A ROUTE OF INJECTION IS potentially EXTREMELY PAINFUL FOR THE PATIENT, anecdotally in the author's experience (unpublished data). Baert et al report haematuria and haemospermia lasting for some weeks after their therapy and the authors emphasize the very high cure rate in chronic bacterial prostatitis if the intraprostatic injections are repeated regularly. Jimenez-Cruz et al report 51 patients with gram-negative chronic bacterial prostatitis treated successfully with 500 mg amikacin and 100 mg tobramycin weekly for 2-4 weeks. Twenty-nine percent failed to respond and 5 patients had relapsed after 6 months. The route was perineal under echographic control into the echogenic zone or external gland. Yamamoto et al emphasize that careful randomized studies with long follow-up are essential to evaluate the merits of the method of intraprostatic injection of antibiotics. The author has not to date seen any written reports or reference to reports of this method in chronic non-bacterial prostatitis."

(Chapter 35, Medical management of chronic non-bacterial prostatitis, Evans DTP, Page 295)

The treatment can therefore be seen as risky but potentially beneficial for CP/CPPS patients if 1) complication rates can be reduced 2) steroids can be supplanted or combined with newer and longer-lasting immunomodulatory, neuromodulatory or anti-inflammatory agents.

 

One of the leading American practitioners of this treatment, Dr Duke Bahn, writes (June 2002):

There appears to be some questions regarding the details of this procedure. First of all, I perform a complete transrectal ultrasound of the prostate to rule out any of the other possible causes, such as prostate cancer or stones in the ejaculatory duct. I use the Hitachi 6500 model, which has a comprehensive color-Doppler capability, as well as tissue harmonic function for better resolution. This is the first unit installed in the USA and no other unit is available at this time. For the injection, I use trans-rectal approach utilizing 22-g fine needle. The mixture is a combination of Gentamycin, Levaquin, Diflucan, Bethamethasone, Lidocaine and Toradol. The hospital pharmacist prepares this mixture within 30 minutes of the actual injection to avoid any precipitation. All together, it is 10 cc's. I infiltrate 3 cc into each lobe of the prostate including the peripheral zone and transitional zone. I also inject 2 cc into each seminal vesicle (if you do not treat the seminal vesicle, the efficacy goes down). I like to repeat the treatment two more times, in two week intervals. I have not encountered any significant complications or side effects so far, even though they may not be known yet. The only expected side effects are hematuria and hematospermia, both of which go away by themselves. Most of my patients have stated that the procedure was quite tolerable with only minor discomfort. All patients fill out the NIH chronic prostatitis symptom score questionnaire on each visit to objectify the effects of the treatment and this information will be used for statistical analysis for future studies. It should be noted that this is a rather unconventional way of treating prostatitis with unknown long term effects. I still encourage you to work with your physician. You should not take this method unless all of your other options are exhausted and your situation becomes desperate. If you have any other questions, please contact me by e-mail or by phone 888-234-0004

Duke K. Bahn, M.D.
Prostate Institute of America
Community Memorial Hospital
Ventura, California 93003

Patients of Dr Bahn relate their experiences on our chronic prostatitis / CPPS forum.

Final word from "The Urology Bible" (Walsh: Campbell's Urology, 8th ed., 2002):

"Intraprostatic Injections

....A number of investigators ([10] Baert and Leonard, 1988; [108] Jimenez-Cruz et al, 1988; [305] Yamamoto et al, 1996) have advocated direct injection of antibiotics into the prostate gland, but this method has never been rigorously evaluated or become popular among urologists." [The Prostatitis Syndromes by J. Curtis Nickel, page 619]