When you are battling an embedded chronic UTI (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.
What causes embedded chronic UTI?
Embedded chronic UTI is a urinary tract infection that is caused by bacterial biofilms in the bladder.
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.
The bottom line, biofilms could be formed in any part of a body and could be caused by many types of bacteria and microorganisms.
Also, I just published a pretty long but informative interview with three experts explaining the link between chronic UTI and bacterial biofilms, check it out!
Bacterial biofilm treatment for embedded chronic UTI
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 reproducing and then hiding under the slime and it protects them from antibiotics and disinfectant chemicals, as well as 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 their surroundings. Teamwork in action!
Who can get embedded chronic UTI
Anybody who has been experiencing UTIs frequently most likely already has biofilms and therefore an embedded chronic UTI could be the right diagnosis.
If you have any type of chronic infection, you could be dealing with bacterial biofilms.
Your chances are even higher if your bladder was operated on or you have (or ever had) a catheter.
What if you only have UTI after sex, does it mean you do not have an embedded chronic UTI and just keep re-infecting? Could be true, but also there is new research indicating that certain vaginal bacteria are capable of triggering E.coli biofilms to start an acute infection.
Some might suggest, bacterial interaction could cause a UTI, not just the mere presence of potentially pathogenic bacteria in your bladder.
That’s why a combinatory, systemic approach to treating UTI is the best. Not only you want to decrease the number of bacteria in your bladder, but also improve vaginal health and the overall gut microbiome.
Bacterial biofilms are undetectable by regular tests
Quite exciting from a scientific point of view, but pretty disturbing if you are trying to fight 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. That’s why it is hard to differentiate between a chronic embedded UTI and a recurrent UTI.
According to new research, members of microbial communities periodically wake up from the state of dormancy and “send out scouts” to test the environment 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 until 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.
However, tests like Aperiomics could identify bacterial strains and we already know that certain strains of E. coli are more virulent and tend to form biofilms. Regular culture, PCR, and even most DNA-sequencing tests only give you the type of bacteria detected.
Antibiotic suppressive therapy basically means that you take the same low dose of antibiotics making sure that bacteria keep on “sleeping” and don’t crawl out of their biofilm to cause trouble.
Some think 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.
However, studies demonstrate that the long-term success of this approach is questionable. Once patients are free of their symptoms and stop the antibiotic therapy, UTIs frequently return again.
For example, bacterial biofilm studies in other clinical areas (chronic spine infection) haven’t proved to be effective when implementing such antibiotic therapy.
Moreover, 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, a 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 are capable of literally turning low doses 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 could be used once antibiotic exposure has ended”.
Aggressive antibiotic therapy
It has been always thought that biofilms can be prevented by early aggressive antibiotic therapy.
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 biofilms, and most of the chronic infections are caused by mature 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.
“You can put a patient on [a high dose] antibiotics, and it may seem that the infection has disappeared,” says Levchenko. “But in a few months, it reappears, and it is usually in an antibiotic-resistant form.”
Preventive antibiotic therapy for chronic embedded UTI
Some hope that low-dose antibiotic therapy could cure chronic embedded UTI. 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 proven efficacy and effectiveness of antibiotics against uropathogenic biofilms adherent to tissues.
Pulsing low dose antibiotics
One of the popular approaches is a combinatory long-term antibiotic suppressive therapy that supposedly attacks bacteria as they emerge. The so-called Dr. Marshall Protocol or (MP) is based on administering very low “pulsating” doses to patients for a prolonged period of time. Marshall, who has a Ph.D. in electrical engineering, invented and tested this protocol to cure himself of a rare disease and then suggested that his protocol could be applied to almost any infectious or inflammatory disease.
There are some researchers that agree with the general approach: cycling of a variety of antibiotics to attack biofilms and persisting bacteria from all angles. In her article “The Riddle of Biofilm Resistance,” Dr. Kim Lewis of Tulane University discusses the mechanisms by which pulsed, low-dose antibiotics are able to break up biofilms, while antibiotics administered in a standard manner (high, constant doses) cannot. However, Lewis herself notes that a concern about patients developing antibiotic resistance given that this protocol would involve short antibiotic cycles and time between cycles free from antibiotics.
However, as per “dr.” Marshall, the key to the protocol is a certain medication (called Benicar) that supposedly strengthens patients’ immune defenses leading to complete eradication of the embedded infection.
At the same time, many practitioners warn about the potential pitfalls of such an approach. For example, Mark London, of MIT, has written a comprehensive analysis of the protocol and concluded that the overuse of macrolides (Zithromax, clindamycin, and others) is known to result in resistant bacteria, and the risk is even higher when antibiotics are combined.
As per Dr. Mercola: “There are certainly times when antibiotics are necessary, but they are widely overused. Every time they are used appropriately in traditional medicine, there are at least 10 to 20 times when they are inappropriately used, and this is what has resulted in antibiotic-resistant bacteria… In the past, I have used antibiotics for rheumatoid arthritis when I was applying Dr. Thomas Brown’s protocol. Even though Dr. Brown clearly helped many thousands of patients with this, after using it for many years I realized that even better results could be achieved without the use of antibiotics.
If infectious agents do underlie disease, which is certainly possible but remains to be proven, antibiotics are not the answer. There are many natural choices for anti-infectives that are much safer and have fewer side effects than antibiotics. For example, for thousands of years, Chinese medicine has been curing infections with herbs, mushrooms, bark, and other natural agents. If you have an infection, your best strategy is to get your immune system into shape by addressing the things I mentioned above, none of which are addressed by the Marshall Protocol.”
My non-medical position on this is similar, I believe the best treatment for a chronic embedded UTI is a systemic holistic approach.
Removal of foreign bodies
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, or an IUD you would want that removed or at least replaced in order to be successful in bacterial biofilm UTI treatment.
A couple of 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.
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 a low pH value (pH 5.2) could decrease the effects of β-lactam antibiotics and increase the 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.
Supplements for biofilm treatment
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. Lactoferrin also naturally found in saliva, breast milk, and the supplement is typically made from cow’s milk. It has a unique ability to reduce free iron that otherwise serves as food for pathogenic bacteria. This is by far my favorite supplement when fighting any sort of infection. It is easy to digest and for most is very well tolerated. This is one of the rare cases when a supplement has a well-studied method of action and we know how it performs in-vivo.
Below are promising substances that have one in common: they have been studied in vitro, meaning that we do not know how their effectiveness would translate from a lab experiment to a living organism model. When you take a supplement orally, it undergoes many changes during a metabolic process and it’s hard to know what molecules and in which concentrations reach the bladder. Nevertheless, here is a list:
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 the ability to move around. Therefore, luteolin or luteolin-rich products as a dietary supplement may be beneficial to control e.coli-related bladder infections.
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 the 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 the particular effects of NAC, folks with the 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 surgery, stop taking N-acetylcysteine 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 acetylcysteine
- 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.
This 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 the 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 the 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, the 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 whose 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.
Enzyme-based supplements with possible anti-biofilm effect:
Choosing a bacterial biofilm treatment supplement
Frankly, there is no “one size fits all” model, each product has it’s own potential benefits and side-effects.
Moreover, there are no clinical studies with any of the above-mentioned supplements for treatment or prevention of UTI. Therefore, we don’t know if it could be effective and at which dose.
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 an obvious 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 from other patients.
As to myself, I first heard about NAC supplements from a naturopathic doctor who uses it in her practice. I have been using a combo of NAC Jarrow 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 & Lactoferrin for 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.
Check with your MD
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 reviews when considering a new supplement.
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 the lower intestines and then ascend into your vagina. This is exactly how vaginal probiotics when taken orally work.