In 1945 Alexander Flemming was awarded a Nobel Prize in “Physiology or Medicine” for his work on the early use and application of antibiotics and in particular his discoveries around Penicillin. I have no issues with Mr Flemming at all I think he was a great man, but I do with his wonder drug. His wonder drug, the marvel of ‘new medicine’ does not sit well with me at all. Primarily because I get a big fat allergic reaction from taking it! Our boy cat recently had an abscess the size of a £2 coin near his tail from fighting the local Tom cat (the 2 puncture wounds indicate the blighter bit him there). The vet gave him a course of Penicillin to reduce the infection and get his temperature down. It has worked a treat and he is back to his usual boisterous self. I was strongly advised that I should not be the one administering him his meds. Sadly this responsibility fell upon my wife’s shoulders. I swell up, go red, blotchy and have difficulty breathing (probably a insight into my future self) if I do come into contact with penicillin! Regardless of my allergies the introduction of antibiotics has saved countless lives, it cannot be argued that they truly have been a wonder drug. However, as human beings we are reaching the point of saturation when it comes to their benefits. The overuse of antibiotics is now widely reported and we are now in an age of “antibiotic resistance.”

Between 2000 and 2010, total global consumption of antibiotics grew by more than 30%. From approximately 50 billion to 70 billion standard units, based on data from 71 countries (1). 20 to 50% of total antibiotic use is deemed to be inappropriate (2). “Inappropriate” can mean either of two things:

1. The use of antibiotics when no health benefit is possible; or

2. The suboptimal use of antibiotics for responsive conditions, such as the choice of drugs with an unnecessarily broad spectrum, incorrect dosage or duration, or poor patient adherence to the prescribed treatment (3).

The U.S. Centre for Disease Control & Prevention (CDC) estimates that “antibiotic resistance” is responsible for more than 2 million infections and 23,000 deaths each year in the United States, with a direct cost of $20 billion (4). In Europe, there are an estimated 25,000 deaths attributable to “antibiotic-resistant” infections, costing €1.5 billion annually in direct and indirect costs (5).

If you are suffering with, or have ever suffered with prostatitis the chances of you taking a course of antibiotics are astronomically high. If you have been diagnosed with bacterial prostatitis through the appropriate testing methods (see below) that are widely recognised, researched and verified then I totally advocate the use of antibiotics to treat the condition. With 90-95% of all cases being non-bacterial it is imperative that the correct tests are utilised to provide a clear diagnosis. The National Institute of Health (NIH) classify prostatitis into the following categories. Note that type III is the most common form and is non-bacterial:

I. Acute bacterial prostatitis

II. Chronic bacterial prostatitis

III. Chronic prostatitis (CP)/Chronic Pelvic Pain Syndrome (CPPS)

a. Inflammatory

b. Noninflammatory

IV. Asymptomatic inflammatory prostatitis

There have only ever been 3 randomized, controlled clinical trials assessing antibiotics in the treatment of CP/CPPS. Ciprofloxacin, Levofloxacin and Tetracycline Hydrochloride were tested against placebos. Although some symptom improvement was observed, the studies failed to show any significant statistical improvement from baseline to 6 weeks. (6,7,8).

In 2014 NICE (National Institute for Health and Care Excellence who provide national guidance and advice to improve health and social care) outlined clear guidelines on antimicrobial stewardship to manage and reduce the unnecessary use of antibiotics. They provided guidelines for primary (GP’s) and secondary (Urologists) healthcare providers:

Primary Healthcare Providers

Prescribe an antibiotic only if there is likely to be a clear clinical benefit.

Secondary Healthcare providers

Do not start antibiotics without clinical evidence of bacterial infection.

If there is evidence or suspicion of bacterial infection, use local guidelines to start prompt, effective antibiotic treatment.

I see patients who have been prescribed antibiotics for months on end. Some patients have been on them for years and others on them indefinitely with no clear diagnosis of any bacterial infection found! Current guidelines indicate that a 4-6 week of antibiotics is standard procedure but if there is no infection found, nor any change in symptoms then ‘other’ treatment modalities must be implemented. So why, oh why oh why is this not the case. Why are there SO many patients who have not had the appropriate testing for bacterial prostatitis on prolonged, repeated dosages with little, if any review of the medication?! Fig 1 is an algorithm outlining the current guidelines for the treatment of CBP (chronic bacterial prostatitis) and CP/CPPS as per the Prostatitis Expert Reference Group (PERG) (9) who were convened in 2013 by Prostate Cancer UK. Standard procedure indicates a 4-6 week course of antibiotics, with a follow up (also at 4-6 weeks) to review medications. If there is a bacterial cause confirmed or if there is a partial response (not graded or measured here for clinical reasoning) then a further course should be considered. If there is no bacterial cause identified and no response to antibiotics then they are to be ceased and other modalities looked into (although sadly there is no mention of manual or physical therapy here!)

PERG recommends the use of testing to determine the presence of bacterial infection and then, in accordance with their guidelines whether to repeat the use of antibiotics or not. They introduced a validating symptom scoring instrument to assist specialists and non-specialists to determine the appropriate and suggested testing methods. The Meares-Stamey 4 and 2 glass tests are clearly advised to determine the presence of bacterial infection, however they only view this as ‘optional’ and not a ‘core’ test.

The 4 glass test involves 10mL of urine in the 1st glass, 10 mL of mid-stream urine (MSU) in the 2nd, prostatic secretions are collected in the 3rd glass post prostate massage and finally post massage urine is collected in the 4th glass

The 2 glass test involves a MSU sample and a post prostate massage urine sample

Surely testing must be imperative to avoid the over and misuse of antibiotics in accordance with NICE and global Antibiotic Stewardship Programs (ASP’s)? How can urologists determine, with confidence whether or not they should repeat or even use antibiotics in the first instance without the appropriate testing? A very disappointing 80% of urologists claimed that they ‘rarely’ (47%) or ’never’ (33%) performed the Meares-Stamey 4 glass diagnostic test (10). So, why is this? Well, the 4 glass test has been called ‘time consuming and costly.’ The alternative is the 2 glass test (as outlined by PERG), it was found that the 2 glass test yielded results in concordance with those of the 4-glass test and was used to predict the correct diagnosis in 96% of cases (11). Surely this should be the first line approach for patients with suspected bacterial and/or non-bacterial prostatitis? The test is less time consuming for all involved, the results almost match those found with the 4 glass test and more importantly it can a lead to a correct diagnosis for the patient. The test must be preformed before any antibiotics are prescribed as this will alter the results and therefore the outcome of the patient treatment program. This in turn reduces the unnecessary over prescription of Ciprofloxacin, Levofloxacin or similar highly potent Fluoroquinolones, which have been linked with an increased susceptibility to C. difficile infection (12) and reports of increased hypersensitivity reactions including tendon, joint and muscle pain, pins and needles, tingling or prickling sensations to name but a few (13,14,15).

So, where does this leave us? Well, I wanted to share an extract with you from the book “Prostatitis and Its Management, Concepts and Recommendations for Clinic Practice” released earlier this year (2016) by Tommasi Cai from the Department of Urology at Santa Chiara Regional Hospital, Italy and Truls E. Bjerklund Johansen from the Department of Urology at Oslo University Hospital. This is a hypothetical conversation between a General practitioner (GP) and a Urologist (UR) regarding a prostatitis patient.

GP. Can I use antibiotics in the management of nonbacterial prostatitis patients?

UR. Yes, the urologists often use antibiotics in the nonbacterial patients, too. However, for the sake of antibiotic stewardship, the use of antibiotics should be limited to patients with confirmed bacterial prostatitis only. The rationale for the use of antibiotics in nonbacterial prostatitis is a strong clinical suspicion of a bacterial infection despite the lack of positive microbiological results. In fact, there are many cases where we are unable to identify specific bacterial strains. Whenever antibiotics are prescribed in nonbacterial prostatitis, the effect should be assessed after two weeks, and antibiotic treatment should only be continued in case of a clinical benefit, otherwise the treatment should be stopped. It is important to avoid the repeated use of antibiotics such as fluroquinolines if there is no obvious symptom benefit or other evidence from clinical chemistry or culture tests that supports and infectious etiology. (16)

This sounds like a practical, contemporary and patient focused approach to the use of antibiotics for a typical CP/CPPS patient. It clearly states that unless there is empirical evidence from the appropriate testing then there is no rationale for repeat, prolonged antibiotic prescriptions. I would love to hear that my patients are being tested for bacterium cultures through the use of the 2 (or 4) glass Stammey test. If there is a bacterial infection let’s treat it, lets go to the heart of the matter and know 100% what we are dealing with. This would certainly indicate a significant shift in the right direction. If there is no infection then antibiotics should NOT be used, period. We already have a global issue with antibiotic resistance, why are we feeding that beast? This is an opportunity to change the way a ‘typical’ CP/CPPS patient is managed. This is an opportunity for a proper diagnosis and the necessary treatment to ensue.

Patients – ask for the appropriate testing to ascertain of there is or is not a bacterial infection present. Request a 2 (or 4) glass Meares-Stamey test

Urologists and Dr’s – is the long term use of antibiotics the right answer for the non-bacterial prostatitis patient? The evidence suggests not. There is a responsibility in primary and secondary healthcare to protect patients from antibiotic resistance. Test that patient, know for sure if there is a need (and in 5-10% of all cases there clearly is) for antibiotics.

We know so much more about pain now, why are we still treating CP/CPPS patients the same way we have been for decades? Let’s step up as a whole patients, primary and secondary healthcare providers and make the required changes to ensure the necessary care and appropriate treatment follows.

Karl Monahan is the owner of The Pelvic Pain Clinic, London. He has been successfully treating male pelvic pain since 2010. His depth of knowledge and personal experience on the subject provides his patients with a compassionate approach that is rarely found. His holistic approach to treating male pelvic pain addresses, lifestyle, diet, exercise, stress management and therapeutic movement. The clinics approach is very much aimed at empowering the patient, teaching them the tools and techniques to manage and reduce their own symptoms allowing them to be the driver in their own recovery and not just a passenger. www.thepelvicpainclinic.co.uk

References

1. Van Boeckel, T. P., Gandra, S., Ashok, A., Caudron, Q., Grenfell, B. T., Levin, S. A., and Laxminarayan, R. 2014. Global Antibiotic Consumption 2000 to 2010: An Analysis of National Pharmaceutical Sales Data. The Lancet Infectious Diseases, 3099(14):1–9. http://doi.org/10.1016/ S1473-3099(14)70780-7.

2. Cizman, M. The Use and Resistance to Antibiotics in the Community. 2003. International Journal of Antimicrobial Agents, 21(4):297-307.

3. Starrels, J. L., Barg, F. K., and Metlay, J. P. 2009. Patterns and Determinants of Inappropriate Antibiotic Use in Injection Drug Users. Journal of General Internal Medicine, 24(2):263-9. doi:10.1007/s11606-008-0859-7

4. Centers for Disease Control and Prevention (CDC). 2013. Antibiotic Resistance Threats in the United States. Atlanta.

5. European Medicines Agency (EMA) and European Centre for Disease Prevention and Control (ECDC). 2009. The Bacterial Challenge: Time to React a Call to Narrow the Gap Between Multidrug-Resistant Bacteria in the EU and Development of New Antibacterial Agents. Stockholm.

6. Alexander RB, Propert KJ, Schaeffer AJ et al (2004) Ciprofloxacin or tamsulosin in men with chronic prostatitis/chronic pelvic pain syndrome: a randomized, double-blind trial. Ann Intern Med 141(8):581-9.

7. Nickel JC, Downey J, Clark et al (2003) Levofloxacin for chronic prostatitis/chronic pelvic pain syndrome in men: a randomized placebo-controlled multicenter trial. Urology 62(4):614-7.

8. Zhou Z, Hong L, Shen X et al (2008) Detection of nanobacteria infection in type III prostatitis. Urology 71:1091-1095

9. Rees J, Abrahams M, Doble A, Cooper A; Prostatitis Expert Reference Group (PERG). (2015) Diagnosis and treatment of chronic bacterial prostatitis and chronic prostatitis/chronic pelvic pain syndrome: a consensus guideline. BJU Int. 2015 Oct;116(4):509-25. doi: 10.1111/bju.13101.

10. McNaughton Collins M1, Fowler FJ Jr, Elliott DB, Albertsen PC, Barry MJ. (2000) Diagnosing and treating chronic prostatitis: do urologists use the four-glass test? Urology 55(3):403-7.

11. Nickel JC, Shoskes D, Wang Y, et al. (2006) How does the pre-massage and post-massage 2-glass test compare to the Meares-Stamey 4-glass test in men with chronic prostatitis/chronic pelvic pain syndrome?. J Urol. 176(1):119-24.

12. Delaney JAC, Dial S, Barkun A and Suissa S. (2007) Antimicrobial drugs and community-acquired Clostridium difficle-associated disease, UK. Emerg Infect Dis

13. Golomb BA, Koslik HJ, Redd AJ (2015) Fluoroquinolone-induced serious, persistent, multisymptom adverse effects. BMJ Case Reports 2015; doi:10.1136/bcr-2015-209821

14. Sousa, Joana; Alves, Gilberto; Fortuna, Ana; Falcao, Amilcar. (2014) Third and Fourth Generation Fluoroquinolone Antibacterials: A Systematic Review of Safety and Toxicity Profiles. Current Drug Safety, Volume 9, Number 2, July 2014, pp. 89-105(17)

15. Stahlmann R, Lode HM. (2013) Risks associated with the therapeutic use of fluoroquinolones. Expert opinion on drug safety Page 497-505 | Published online: 07 May 2013

16. T. Cai, T.E. Bjerklund Johansen (eds.), Prostatitis and Its Management: Concepts and Recommendations for Clinical Practice, DOI 10.1007/978-3-319-25175-2_15B p.14