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 A Summary of 8 Antibiotic Studies

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Andi2016

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PostSubject: A Summary of 8 Antibiotic Studies    Sat Jul 09, 2016 8:02 pm

For anyone interested, here is a brief summary of 8 antibiotic trials for IC/PBS/OAB conducted between 1995 and 2013.   If you’ve come across other antibiotic studies for IC/PBS/OAB/chronic prostatitis etc, please post them below.


STUDY 1, 2013:  ‘Lengthy antibiotic treatment to resolve recalcitrant OAB’.  Authors: Swamy S., Gill K., Kupelian A., Sathiananthamoorthy S., Horsley H., Collins L. & Malone-Lee J.
http://www.ics.org/Abstracts/Publish/180/000619.pdf

Study:  351 female chronic LUTS patients were treated with high-dose oral antibiotics between 2010 and 2012.  LUTS signs and symptoms measured included urgency, voiding dysfunction, stress incontinence, pain and pyuria.  The mean duration of treatment was 279 days.

Outcome:  Regression analysis over the treatment period showed significant reduction in 24-hour frequency, urgency, voiding symptoms, pain and pyuria (white blood cells).



STUDY 2,  2011:  ‘Treating OAB with antibiotics’, Authors: Gill K., Khasriya R., Kupelian A., Brackenridge L., Horsley H., Sathiananthamoorthy S. & Malone-Lee J.
http://www.ics.org/Abstracts/Publish/106/000112.pdf

Study:  440 patients (380 females and 60 males) were followed through a 7-year observational cohort study between 2003 and 2010.  Of the total group, 147 had over active bladder (OAB) and pyuria and were treated with antibiotics (Nitrofurantoin and cephalexin), antimuscarinics and bladder training.  212 had OAB and no pyuria and were treated with only antimuscarinics and bladder training.  81 had OAB and developed pyuria during the study, and were treated with antibiotics at this point.  The majority of patients entered the study being MSU culture negative:  OAB with pyuria group – 75% negative; OAB without pyuria group – 88% negative; and OAB who developed pyuria during the study group – 85% negative.


Outcome:  There was a significant improvement in all symptoms in all groups over the treatment periods.  Antibiotic efficacy was demonstrated with clearance of pyuria in the OAB patient group with pyuria at presentation.  The OAB group who received antibiotics later in the study took the longest to recover, but improved significantly once treated with antibiotics.  The OAB without pyuria group, who received only antimuscarinics and bladder training, recovered the fastest.

Questions:  The OAB without pyuria group recovered fastest receiving antimuscarinics and bladder training only.  Could this suggest infection was not involved in this patient group and the pyuria identified in the other 2 patient groups demonstrates it is an important sign of infection?  



STUDY 3, 2010:  Decreased nanobacteria levels and symptoms of nanobacteria-associated interstitial cystitis/painful bladder syndrome after tetracycline treatment’, Authors:  Zhang QH., Shen XC., Zhou ZS., Chen ZW., Lu GS. & Song B.
http://www.ncbi.nlm.nih.gov/pubmed/19760079

Study:  A group of 27 IC/PBS patients underwent cystoscopy.  Bladder biopsies and urine samples were obtained and cultured for nanobacteira using lengthy techniques by Ciftcioglu and Kajander, indirect immunofluorescent staining and transmission electron microscopy.

Outcome: 11 of the group showed growth of microbes identified to be similar to nanobacteria that were suggested to be pathogenic.   All 11 patients were treated with a combination of intravesical instillations (twice weekly) and oral (daily) tetracycline for 3 months.    Follow-up biopsies and urine samples showed levels of nanobacteria decreased dramatically after tetracycline treatment and 100% of patients reported a significant reduction in the severity of IC/PBS symptoms.    Another 5 patients, who tested positive for bacteria other than nanobacteria, were treated accordingly and reported a statistically significant improvement in symptoms.  As the samples during this study were cultured for the most frequent known urogenital pathogens, it was suggested that testing be performed to exclude the many potential pathogens that could be involved in those with IC/PBS.    



STUDY 4, 2004:  ‘Urinary urgency and frequency, and chronic urethral and/or pelvic pain in females. Can doxycycline help?’, Authors:  Burkhard F.C., Blick N., Hochreiter W.W. & Studer U.E.
http://www.ncbi.nlm.nih.gov/pubmed/15201781

Study: 103 female chronic LUTS patients were tested using urethral and cervical/vaginal swabs, serum analysis, urine examination and culture, and bladder barbitage.  Cystoscopy found all patients had trigonal leukoplakia (white patches at the base of the bladder), with 15% having an infectious organism identified through culturing and 30% showing leukocyturia (pus cells).

All 103 patients were treated with doxycycline and a vaginal antimicrobic and/or antifungal agent.  Sexual partners were simultaneously treated with the same doxycycline regimen.

Outcome:  After a four week treatment period with doxycycline and vaginal hexetidine, 71% of women reported being symptom-free or having a reduction in symptoms.  The simultaneous treatment of the sexual partner was attributed to the success rate in the study, but was not proven.

Questions:
1. Could a longer treatment with doxycycline, vaginal antimicrobic and/or antimycotic address bacteria with the ability to evade antibiotic attack through swapping between dormant and active states or forming protective biofilm?



STUDY 5, 2000:  ‘Association of chronic urinary symptoms in women and Ureaplasma urealyticum’, Authors:  Potts J.M., Ward A.M. & Rackley R.R.
http://www.ncbi.nlm.nih.gov/pubmed/10736488

Study:  48 patients with LUTS underwent urinalysis and culture screening for intracellular bacteria for U. urealyticum and Mycoplasma hominis.  Those testing positive were treated with doxycycline, ofloxacin or erythromycin for 7 days or a single dose of azithromycin.

Outcome:  Nearly half (48%) tested positive for U. urealyticum (22 in 48) and Mycoplasma hominis (1 in 48).  Out of the 23 patients treated with antibiotics, 91% reported a statistically significant improvement in symptoms.

Questions:  
1. A 7-day course of antibiotics is designed to treat acute infections.  When considering the possibility of chronic infection, would a short 7-day course be an adequate treatment?  



STUDY 6, 2000:  ‘Pilot study of sequential oral antibiotics for the treatment of interstitial cystitis’, Authors:  Warren J.W., Horne L.M., Hebel R., Marvel R.P., Keay S.K. &  Chai T.C.
http://www.ncbi.nlm.nih.gov/pubmed/10799160

Study:  50 IC patients were formed into 2 groups, with one receiving an 18 week course of sequential antibiotics (rifampin, doxycycline, erythromycin, metronidazole, clindamycin, amoxicillin and ciprofloxan for 3 weeks each).  The second group received a placebo.   During the study period, 64% of the antibiotic group and 56% of the placebo group received additional IC therapies, including analgesia, bladder hydrodistension and urethral dilation.   In addition, 28% of the placebo group and 12 % of the antibiotic group received antibiotics from another doctor for other health conditions arising during the study (ie respiratory tract infection).

Outcome:  55% of the antibiotic group reported overall improvement in symptoms.  30% of the placebo group also reported overall improvement.

Questions:  
1. This is confusing.  Despite 85% of all participants reporting overall improvement, the study concluded it was “not a highly effective therapy for interstitial cystitis”.  Why is this?  In contrast to this is the Editorial Comment by Jenny J Franke, Dept of Urological Surgery Vanderbilt University Medical Centre, Nashville, Tennessee.  She says the study highlighted specific IC patients in her practice who claim symptoms improve with long-term antibiotics.  She goes on:  “What are we treating?  If the etiology of bladder pain and irritative symptoms in the majority of patients with interstitial cystitis is a deficient glycosaminoglycan layer, a urinary toxin or non-infectious bladder inflammation, broad-spectrum antibiotics are unlikely to provide significant benefit.  However, if a subset of these patients have an atypical infection, which I believe is possible, identifying this organism would provide a clue to the pathophysiology, a marker of disease and a basis for treatment.”   Jenny Franke appears to be vocal linking bacteria (namely Chlamydia Pneumoniae) to IC in reports leading up to this time, but goes quiet on the topic after joining the Jennie Stuart Medical Centre, Kentucky, in 2001.

2. The double-blind randomization and distribution of medication was developed and maintained by Linda Hultgren.   A connection to Scott Hultgren?    

3. Is this study flawed from the start?  Considering it’s an antibiotic study, why were patients and placebo groups still receiving additional IC therapies for their symptoms?  This confuses what could be responsible for the reported results.  

4. 30% of the placebo group noted overall improvement.  However, 28% of the placebo group received antibiotics during the study period for other health conditions.  Does this impact on it being a true placebo group?     

5. Knowing what Scott Hultgren has discovered about Intracellular Bacterial Communities (IBCs) and QIRs in those with recurrent UTIs, when testing for bacterial causation in IC/PBS, could it be argued that an 18 week antibiotic treatment is too short to provide realistic results?  Under these circumstances, could  antibiotics rotated every 3 weeks be expected to effectively treat embedded UPEC and persistent IBCs and QIRs.



STUDY 7, 1995:  ‘Dormant microbes in interstitial cystitis’, Authors:  Domingue G., Ghoniem G., Bost K., Fermin C. & Human L.G.
http://www.ncbi.nlm.nih.gov/pubmed/7869536

Study:  Bladder biopsies were performed 29 people made up of 14 IC patients and 15 controls.  PCR testing was used to identify potential bacterial involvement.  

Outcome: Gram-negative bacteria were identified in 29% of the IC patient group, whereas no bacteria were identified from any in the control group.  An unrecognised form was isolated in 100% of the IC patient group and 7% of the control group, suggesting possible involvement of an unclassified microbe.  

Questions:
1. Since PCR testing is limited to known bacteria that the testing is programmed to look for, does this prove bacteria falling outside these parameters are not implicated?

2. Has evidence of the existence of this curious and unclassified microbe ever been examined?  Were follow-up studies conducted?   In the report the unclassified form was described as to “contain nucleic acids and resemble cell wall-deficient bacteria in gross morphology; however, their swirled myelin-like ultrastructure is unusual”.    There is mention of a 1997 study by Domingue titled ‘Occult Infection in Interstitial Cystitis’, but I was unable to locate it online.



STUDY 8, 1995:  Anti-anaerobic antibiotic use in chronic inflammation, urgency-frequency, urge incontinence and in interstitial cystitis syndromes. Presented at the meeting of Women’s Urological Health Program, National Institute of Diabetes, Digestive, and Kidney Diseases Research Symposium On Interstitial Cystitis, Bethesda, Maryland, January 9-11, 1995, Durier, J. L.

This study is referenced in a number of other antibiotic-related papers.  It reported a high success rate treating LUTS patients with antibiotics, with 27 out of 27 said to be cured after receiving 5 sequential antibiotics.   I haven’t been able to locate this study online.
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PostSubject: Re: A Summary of 8 Antibiotic Studies    Sun Jul 10, 2016 3:11 am

Wow! It looks like this has some promise! I just posted an article from a few years ago in the Journal Nature that talks about gene therapy for IC. I believe if there was more genomic research into IC and we sequenced the genome of Lots of IC patients and also the Genome of lots of gelato controls, then we would be able to search for common differences between the two groups and hopefully close the gap by editing the genome of the IC patients to some how match up with healthy controls. What do you think?
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PostSubject: Re: A Summary of 8 Antibiotic Studies    Sat Jul 16, 2016 11:39 am

Thanks Joseph - I read the link you supplied about the gene therapy. I haven't read much about this before, but gene therapy is similar'ish to stem cell therapy? From my understanding, the aim of the suggested gene therapy is to deliver anti-nociceptive products that will turn off pain signals. So this isn't getting to the root of the problem, and it won't stop IC/PBS developing in millions of women and men in the first place, but it's a line of research that would interest drug companies, I bet.
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