Could short-course antibiotics for UTIs, which appear to promote resistant bacteria and bacterial reservoirs, possibly lead to the development of IC/PBS?
The following is one scenario that appears common for someone who has developed IC/PBS:
1. A woman develops an acute UTI. Her GP sees evidence of infection from dipstick examination and may send the sample off to the labs for verification. If she’s in the UK, the typical first line treatment will be a 3 day course of Trimethoprim. If she’s in Australia, first line treatment will usually be a 5 day course of Trimethoprim. The lab report confirms an e-coli infection, which is said to be responsible for more than 85 percent of all UTIs, according to a 2012 report in the journal Emerging Infectious Diseases. Her symptoms resolve as expected.
2. Some months later she returns to her GP with another acute UTI. She is again prescribed a short course of Trimethoprim and her symptoms appear to resolve. In some cases however, the appearance of resolution is illusory.
3. Thereafter, infections start to recur more frequently. Different antibiotics may be tried. Mainstream physicians follow the prescribing guidelines that advocate 3, 5, max 7 days, depending on the antibiotic. (Generally doctors consider these episodes new infections, possibly stemming from the gut or vagina). Occasionally a nightly low dose antibiotic will be advised for a period of 3-6 months as a prophylactic to keep the urine ‘sterile’ to prevent re-infection. Even with this longer regime she has breakthrough infections.
Note: Important new research led by Scott Hultgren, Prof of Molecular Biology, Washington University St Louis, has found this common pattern of recurrent UTIs to be caused by uropathogenic e coli (UPEC). He has demonstrated that very early on during the initial acute UTI, a UPEC forms bacterial reservoirs inside the bladder, which then go on to re-infect the host:
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UPEC utilizes complex mechanisms to subvert innate defenses to persist and cause disease. The ability of UPEC to invade into superficial cells of the bladder has been shown to be a critical mechanism in the ability of UPEC to establish a persistent infection” (1)
Hultgren’s research suggests that the typical short-course Trimethoprim that women receive is ineffective in resolving these infections:
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Ten days of trimethoprim-sulfamethoxazole (SXT) therapy reduces urinary recurrences and eradicates fecal colonization, whereas 3 days of SXT treatment has no effect over a twenty-eight-day observation period despite clearing fecal colonization acutely. Interestingly, SXT is unable to eradicate bacteria from the bladder reservoir even after a 10-day treatment regimen, thus demonstrating that the bladder reservoir can persist even in the face of long-term antibiotic therapy.” (2)
His research has also implicated prophylactic antibiotics in the development of antibiotic-resistant strains of UPEC, which women with recurrent UTIs are so often prescribed:
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Patients with chronic urinary tract infections are commonly treated with long-term prophylactic antibiotics that promote the development of antibiotic-resistant forms of uropathogenic Escherichia coli (UPEC), further complicating treatment.” (3)
Other researchers are finding that for some infectious diseases, much higher antibiotic doses are required to eradicate bacteria completely. For example: Professor Sun Nyunt Wai, Umeå University speaking of cholera says:
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Antibiotics are no problem if the dosage is right. But if it isn’t high enough, bacteria counterattack with an alternative strategy,” (4)
From a Research Gate publication:
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Sub-lethal concentrations of antibiotics increase mutation frequency in the cystic fibrosis pathogen Pseudomonas aeruginosa” (5)
4. At some point in the course of the patient’s recurrent infections, it is not unusual for both dipstick and laboratory analysis to start demonstrating no evidence of infection. Guided by these tests, doctors assume the infection has been successfully treated, in spite of her on-going symptoms. In the prevailing acceptance of the belief that absence of evidence is evidence of absence a GP has to make assumptions to try and establish a diagnosis. Perhaps she has developed a sensitive bladder? Could the lining of her bladder have been compromised? Maybe she’s under stress and her problem is psychological?
On the face of it this is inadequate. Knowing her history and her symptoms, would it perhaps be fair for the practitioner also to question the accuracy of these age-old tests? The following study from the Research Department of Clinical Physiology, University College London Medical School has refuted the accuracy of dipstick and standard urinalysis:
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Despite official guidelines and widespread use these tests cannot be considered appropriate for diagnosing urinary tract infection in patients with lower urinary tract symptoms, and should be abandoned in this context." (6)
Another study from the Loyola University Chicago, which has recently disproved the common belief that urine is sterile:
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Traditional tools for urinary bacterial assessment, including urinary dipsticks and standard urine cultures, have significant limitations that restrict the information available to clinicians" (7)
4. At this point in the scenario, antibiotic treatment for her recurrent UTIs has ceased. Her symptoms often intensify, with chronic pain, frequency, nocturia etc., and pain may involve areas seemingly unrelated to the bladder, eg.inner thighs, supra-pubic, legs etc. Any further testing offered continues to indicate that an infectious cause is not involved. The patient may then be referred to a specialist, who may conduct standard urological investigations (which can worsen symptoms). If nothing significant is found , which is often the case, a diagnosis of IC/PBS is made as a default. (Hunner’s ulcers, considered a hallmark for IC, are rare, typically in less than 7% of patients)
5. She has now been labeled with a chronic, painful condition that is little acknowledged and poorly understood. She is offered treatments for symptoms management, which are riddled with unpleasant side effects and unacceptably high failure rates. She may even be referred to a psychologist and will sometimes be offered pain management. After years of unrelenting pain, bladder removal is an option. It is a sad story and one that is being experienced by far too many to be ignored.
After considering the information above, I would be glad if you could please give your views on a couple of questions I have:
Q. Would you give any credence to the notion that if acute UTIs are only partially treated with short-course and prophylactic antibiotics, there is risk of:
a) the development of resistant strains?
b) the development of bacterial reservoirs?
Q. Is it a possibility that undertreated UTIs may lead to complications such as resistant strains and bacterial reservoirs, which then lead to the development of IC/PBS?
Q. Based on the above information, could it be argued that UTIs should always be treated much more aggressively, as opposed to popular 3 day courses?
Q. Do you think current testing is adequate in identifying UPECs and bacterial reservoirs, which are now implicated in recurrent and chronic UTIs?
Q. Since IC is a rare consequence of the above scenario, will you be investigating other factors that might predispose someone to develop IC/PBS?
1.
http://www.pnas.org/content/101/5/1333.full.pdf 2.
http://www.ncbi.nlm.nih.gov/pubmed/12438384/3.
http://www.ncbi.nlm.nih.gov/pubmed/220894514.
http://sciencenordic.com/weak-antibiotic-doses-undermine-our-body%E2%80%99s-defences5.https://www.researchgate.net/publication/233837375_Sublethal_concentrations_of_antibiotics_increase_mutation_frequency_in_the_cystic_fibrosis_pathogen_Pseudomonas_aeruginosa
6.file:///C:/Documents%20and%20Settings/Owner/My%20Documents/Downloads/Inadequacy%20of%20Dipsitcks%20and%20Microsopy%20(2).Pdf
7.https://www.researchgate.net/publication/277027063_The_New_World_of_the_Urinary_Microbiome_in_Women