When you are battling a chronic urinary tract infection, it is easy to imagine that you are trying to kill a number of single-celled organisms floating around, however, what you really need is biofilm treatment for UTI.
Basically, bacteria team-up against you and your treatment strategies have to account for that.
#1: What are bacterial biofilms?
What are bacterial biofilms? In their 2003 Science paper, Anderson et al. reported that E.coli form pod-like bulges on the bladder surface that protect the Individual bacteria from your immune system and antibiotics.
“When bacteria are under stress—which is the story of their lives—they team up and form this collective called a biofilm. If you look at naturally occurring biofilms, they have very complicated architecture. They are like cities with channels for nutrients to go in and waste to go out.”, according to Andre Levchenko, Ph.D., Johns Hopkins University.
UTI-sufferers are not alone: bacteria form biofilms everywhere in our body: lungs, bladder, stomach, and even artificial implants (such as an artificial joint) or catheters. Bottom line, biofilms could be formed in any part of a body and could be caused by many types of bacteria and microorganisms.
#2: Bacterial biofilm treatment for UTI: an uphill battle
The worst news is that bacteria growing in a biofilm could become up to 1,000 times more resistant to antibiotics than a single-celled organism.
Think of biofilm as a type of slime that consists of polysaccharide, protein, and DNA. Bacteria are producing and then hiding under that slime and it protects them from antibiotics and disinfectant chemicals as well as biofilm helps them resist your body’s natural defense system.
Besides harboring pathogenic bacteria, biofilms are also behaving differently than any given single bacteria using so-called “quorum-sensing-regulated mechanisms”. This allows the bacteria to communicate with each other and adjust their behavior based on the surroundings. Teamwork in action!
#3: Who can get biofilms
Anybody with a chronic UTI most likely already has biofilms.
If you have any type of chronic infections, you could be dealing with bacterial biofilms.
Your chances are even higher if your bladder was operated or you have or ever had a catheter.
#4: Bacterial biofilms are undetectable by regular tests
Quite exciting from a scientific point of view, but pretty disturbing if you are trying to fight an infection is the ability of the bacteria to enter a latent state during harmful (for them) conditions.
The worst thing is that not only this keeps bacteria alive in a long run, but also makes them undetectable for tests, and without obvious symptoms in a patient.
According to new research, members of microbial communities periodically wake up from the state of dormancy and “sending out scouts” to “test the environment” to check it out and see if it is the right time for them to start growing again. This ability called “quorum sensing”.
Quorum sensing is a form of bacterial cell-to-cell communication whereby bacteria secrete and detect signaling molecules known as autoinducers
In this scenario, if the “scouts” sense that the environment is now hospitable, they would signal the remaining cells to wake up and start multiplying, which will result in detectable UTI symptoms.
However, if the “scouts” bring back bad news, the colony will “lay low” till the next opportunity and would be not detectable in dipstick urine analyses.
That’s why diagnosing bacterial biofilms with standardized tests is next to impossible.
Bacterial biofilm treatment for UTI: antibiotics
#5: Traditional thought: antibiotic prevention
It has been always thought that biofilms can be prevented by early aggressive antibiotic therapy.
Others thought that antibiotic suppressive therapy could work for biofilm treatment for UTI, which basically means taking low doses of antibiotics for prolonged periods of time to avoid an active infection.
#6: Aggressive antibiotic therapy doesn’t work
In vitro experiments showed that young biofilm could be easily cleared by antibiotic treatment compared to the matured biofilm. Therefore early and aggressive antibiotic treatments are recommended for bacterial biofilm treatment of UTI.
However, it’s difficult to know if you are about to develop the biofilms, and most of the chronic infections are caused by matured biofilms which are usually difficult to eradicate with antibiotic treatment.
In fact, more and more clinical observations and experimental studies indicate that antibiotic treatment alone is in most cases insufficient to eradicate biofilm infections.
Moreover, what in some cases thought as an antibiotic-resistant case of UTI, could be in fact an infection caused by bacterial biofilms since biofilms could be up to 1,000 times more resistant to antibiotic treatment than single-celled bacteria.
#7: Low dose antibiotic therapy is not working
Some hope that low-dose antibiotic therapy could prevent UTI from recurring. Others think, that all it could be doing is just delaying the onset of the infection.
For example, when bladder epithelial cells from 23 spinal cord injury patients were examined, they showed the presence of adherent bacterial biofilms in 96% of the cases. At the very same time when the specimens were collected, most of the patients were receiving antimicrobial therapy, primarily trimethoprim-sulfamethoxazole, which didn’t make any difference in terms of the bladder colonization.
As one of the researchers commented on the results of the study: “The large number of bacteria that emerged with highly virulent and potentially multi-drug resistant characteristics, especially Enterococcus faecalis (33% of isolates), was of concern. These findings raise questions about the proved efficacy and effectiveness of antibiotics against uropathogenic biofilms adherent to tissues.”.
Simply put, the antibiotics seem to be not working when you are treating bacterial biofilms.
#8: Low dose antibiotics are feeding bacteria!
Antibiotic suppressive therapy basically means that you take a low dose of antibiotics making sure that bacteria keep on “sleeping” and don’t crawl out of their biofilm to cause trouble.
Shockingly, there is a study suggesting that bacterial biofilms actually thrive when given a low dose of antibiotics leading to persistent chronic infections. Researchers from the University of Southern California and the Oak Crest Institute of Science found a link between chronic lung, sinus and ear infections and low doses of antibiotics.
“Once the biofilm forms, it becomes stronger with each treatment of antibiotics,” said Paul Webster, Ph.D., lead author, senior staff scientist at USC and senior faculty at the Oak Crest Institute of Science.
In an experiment, they demonstrated how pathogenic bacteria after forming a biofilm is capable of literally turning low dose of antibiotics into glycogen to fuel their further growth.
“With an introduction of antibiotic produced glycogen, the biofilms have an almost endless food source that was be used once antibiotic exposure has ended”. Wow! Could there be any better reason to consider an alternative option for bacterial biofilm treatment for UTI?
#9: Removal of foreign bodies such as catheter to combat biofilms
As discussed earlier, any foreign object becomes a surface where bacteria can build their
“home”. Bacteria are able to stick to metals, plastics, and stones even stronger than to your bladder lining cells.
Any foreign body provides an ideal surface for biofilms to form on. If you have been experiencing chronic UTIs and have a stone, a catheter, or bladder mesh you would want that removed or at least replaced in order to be successful in bacterial biofilm UTI treatment.
A couple important points about changing a catheter from Nature.com:
- Change of the infected catheter is not difficult; however, the time to change is important.
- It is recommended to change the infected UC after 48 h of adequate and sensitive antibiotic treatment to minimize the bacterial concentration in the bladder and urinary tract; otherwise, the new UC would be colonized quickly by the bacteria to form a new biofilm.
#10: PH-level during antibiotic treatment
It is well known that infection could lead to inflammation, which results in faster metabolism and increased consumption of oxygen. If oxygen supply could not meet the demand, glycolysis will be activated leading to acidosis, and the effects of antibiotics could be affected by pH values.
It has been reported previously that low pH value (pH 5.2) could decrease the effects of β-lactam antibiotics and increase effects of rifamycin SV.
Therefore make sure to alkalize your urine during antibiotic treatment to have a chance in the battle of biofilm treatment for UTI.
#11: Non-antibiotic biofilm treatment for UTI (supplements)
A promising strategy may be the use of enzyme molecules that can dissolve the biofilm matrix as well as quorum-sensing inhibitors that increase biofilm susceptibility to antibiotics.
Quorum sensing inhibitors
A range of solutions that when applied weaken the ability of bacteria to sense and react to surroundings called quorum sensing inhibitors.
Various small molecules
While there is a range of the small molecules that have been shown to inhibit QS at the various stages, very few have been clinically tested and even fewer are available commercially.
Azithromycin topically has been used to improve bacterial biofilms susceptibility to antibiotics. Some research demonstrated that a combinational therapy of Azithromycin and ciprofloxacin has promising results against biofilm-associated UTIs, especially in catheter-induced infections.
Lactoferrin, an antimicrobial peptide which anti-biofilm efficacy has been demonstrated in various studies and it is considered to be effective against infections of the urinary tract.
Parthenolide (isolated and purified from Chrysanthemum parthenium plant extract) as a natural product showed also an effect of disrupting pre-established biofilms.
S-adenosyl-methionine (SAM) Naturally occurring brominated furanones produced by algae have been shown to be effective against biofilm formation in a variety of bacteria such as V. cholerae and E. coli.
Baicalein promoted proteolysis of TraR protein in E. coli, strongly suggesting that its biofilm-inhibition properties might be due to QS inhibition
Luteolin, a dietary polyphenolic flavonoid has been confirmed as a potential antimicrobial agent. It significantly decreased the attachment and invasion of E.coli in human bladder epithelial cells via a range of effects on the bacteria including its ability to form biofilms and ability to move around. Therefore, luteolin or luteolin-rich products as a dietary supplement may be beneficial to control the e.coli-related bladder infections.
N-acetylcysteine (NAC): most popular small molecule
N-acetylcysteine (NAC), a derivative of the amino acid l-cysteine, is a potent thiol-containing antioxidant that serves as a precursor of glutathione synthesis. NAC molecules help the immune system by destroying intermolecular or intramolecular disulfide bonds of bacterial proteins.
NAC demonstrated antimicrobial properties against both Gram-positive and Gram-negative bacteria.
Additionally, an antibiofilm activity has been reported, including reduction of bacteria adhesion, reduction of extracellular polysaccharide production and disruption of mature biofilms.
NAC is a known drug widely applied in a number of different clinical conditions:
- Chronic bronchitis
- Acetaminophen overdose treatment
- Chemotherapy-induced toxicity treatment
- Tissue regeneration, mostly in orthopedic and dental implants
- And even psychiatric disorders.
In general, NAC considered to be extremely safe for most people with little to no side-effects however, but it’s a good practice to consult with a physician before starting on NAC.
Also, due to particular effects of NAC, folks with following issues must exercise caution when taking NAC:
- Asthma patients: N-acetyl cysteine might cause bronchospasm in people with asthma
- If you are already taking blood thinners or have a bleeding disorder when your blood does not form a clot. N-acetyl cysteine might slow blood clotting and therefore it could increase your risk of bruising and bleeding.
- If you are going for a Surgery. Stop taking N-acetyl cysteine at least 2 weeks before a scheduled surgery since it might slow blood clotting and this might increase the risk of bleeding during and after surgery.
- Obviously, do not take NAC if you are allergic to acetyl cysteine
- One study reported that very high doses (up to 40 times higher than a regular therapeutic dose) of NAC caused pulmonary arterial hypertension (PAH) in mice.
In general, NAC is widely used in medicine since early 2000 and so far has been reported as well-tolerated.
While there are many well-documented uses of NAC due to its antimicrobial effects, there is only one UTI-specific study that I was able to find. The study compared a preventive regimen of two groups: one was using a low dose of antibiotics, while the other group was taking D-Mannose, NAC and Morinda citrifolia fruit extract.
The study showed no significant difference in results between two groups and suggested that non-antibiotic therapy was as effective (and better received with fewer side-effects) as the antibiotic therapy.
Garlic and bacterial biofilms
Many studies have researched effects of garlic on biofilm formation and the results are quite promising, however, we still need to wait for many more successful clinical studies before we can get FDA to agree that garlic could help in our fight against chronic UTIs.
In one study, extract of raw garlic was able to reduce biofilm formation in a lab (in vitro) and disabled bacterial quorum-sensing functions of Pseudomonas aeruginosa (opportunistic bacteria that is responsible for causing persistent and recurrent UTIs among catheterized patients).
The same researchers verified the effects of garlic in a living organism by feeding fresh garlic extract to infected mice. The mice consumed garlic for five days and then their kidneys were evaluated.
Mice that did not receive garlic extract, developed a severe kidney infection, while mice treated with garlic had only mild symptoms with significantly lower renal bacterial counts compared to test group animals.
When bacterial samples from both groups of mice were later evaluated, it was established that the group treated with garlic had significantly less bacterial growth in comparison with the test group who’s biofilms grew more sticky and thick in absence of garlic treatment.
In general, the consensus is that garlic has the prophylactic potential to prevent UTIs caused by biofilm cells of P. aeruginosa in catheterized patients.
And even if you are taking antibiotics, supplementing with garlic could possibly increase their efficacy.
Other commercial products with potential anti-biofilm effect
#12: How to choose bacterial biofilm treatment supplement?
Frankly, there is no “one size fits all” model, each product has it’s own potential benefits and side-effects. As you can see, all products listed above are considered “supplements”, meaning that they have not been evaluated and recognized by FDA for their beneficial effects, either for their side-effects, and that’s why most of them have very vague labels.
As you might know, it is very expensive to turn something that works into an official FDA approved drug and it is only a viable option if you could patent the drug afterward. Therefore, there is a big “problem” with most above-mentioned molecules: they are found in nature and have little commercial value for companies that could afford drug trials.
However, for, consumers, this presents another issue: we can only rely on our own experience or reviews of patients like ourselves (mostly with no help from frequently uninformed doctors).
As to myself, I have been using a combo of NAC NOW (once the bottle is over I will switch to NAC Jarrow to try it out since it has pure NAC without other microelements), probiotics & prebiotics preventively for over a year now with no apparent side-effects. I personally chose NAC for its price and well-documented efficacy but other supplements have plenty of positive reviews as well.
When choosing a supplement, I also wanted to go with something that could benefit my overall health so I do not feel like I’m constantly fighting UTI and, instead, doing good for my whole body.
#13: Anyway, do check with your MD & Amazon
If you decide to start a new supplement, please ask your physician. New side-effects are constantly discovered and it might very well be that a supplement could interfere with other drugs you are taking or could be not advisable given your particular health condition.
Also, do read comments on Amazon. Especially, negative. While some folks out there could be experiencing side-effects that have nothing to do with the supplement, the wisdom of the crowds is still very valuable. There are plenty of health forums, of course, but I find it beneficial when reviews are directly linked to a particular brand and their product.
But wait, there are good bacteria, too!
I’m (as well as many of you) super concerned about cleanliness. And rightly so, since most UTIs are caused by bacteria that live in our own poop.
But as you might know, there are beneficial bacteria everywhere on our body (including our anus and genitals) as well. Every day good bacteria are helping you to fight the battle with opportunistic bacteria, such as e.coli to keep you healthy.
It’s important that you do not use harsh chemicals in your personal daily hygiene and keep on taking probiotics to re-populate your genitals (yeah, genitals) with good bacteria.
When you take a certain type of probiotic, believe it or not, the freeze-dried bacteria in from the pill come alive and travel all the way through your digestive tract to lower intestines and then ascend into your vagina. This is exactly how vaginal probiotics when taken orally work.