Urinary Tract Infections In The United States
There are more than 18 million physician visits for the treatment of UTIs each year in the US, and over 3 million patients experience two or more UTI per year. For these recurrent UTI patients, antibiotic regimens typically suppress symptoms, but the infections recur within 30 to 90 days. These patients depend heavily on antibiotics.
A survey of 102 urologists revealed that about 24% of recurrent UTI patients are on suppressive antibiotic regimens consisting of 1-4 months or more of daily antibiotic use. A separate 57% of recurrent UTI patients self-medicate their symptoms with antibiotic refills. These data demonstrate that approximately 80% of recurrent UTI patients routinely take antibiotics to alleviate their UTI symptoms. Antibiotics do not reduce recurrences, but only alleviate acute symptoms.
The predominant bacteria causing recurrent UTI are Escherichia coli and Klebsiella pneumoniae. As of 2012, more than 20% of the Escherichia coli and/or Klebsiella pneumoniae identified from bacterial infections are resistant to all of the antibiotics used to treat recurrent UTI, except for the carbapenems. And as of 2015, 25% of Klebsiella pneumoniae cultures among patients in a large network of long-term acute care hospitals are resistant to carbapenems.
Vaccine Strategy For Utis From Abraham Lab
Goodbye UTIs: Duke scientists develop vaccine strategy for urinary tract infectionsIn tests in mice, the vaccine administered directly to the bladder cleared bacteria
DURHAM, N.C. Anyone who has ever developed a urinary tract infection knows that it can be painful, pesky and persistent. UTIs have a high recurrence rate and primarily afflict women as many as 50% of women will experience at least one UTI during their lifetime.
However, what if patients could take a vaccine that would prevent future UTIs? In a March 1 study in the Proceedings of the National Academy of Sciences, Duke researchers describe a new vaccination strategy that they think could re-program the body to fight off the bacteria that cause urinary tract infections successfully.
Although several vaccines against UTIs have been investigated in clinical trials, they have so far had limited success, said Soman Abraham, Ph.D., Grace Kerby Distinguished Professor of Pathology, Immunology and Molecular Genetics & Microbiology in the School of Medicine and senior author on the paper.
There are currently no effective UTI vaccines available for use in the U.S. in spite of the high prevalence of bladder infections, Abraham said. Our study describes the potential for a highly effective bladder vaccine that can not only eradicate residual bladder bacteria, but also prevent future infections.
In addition to Abraham and Wu, study authors include Chunjing Bao and R. Lee Reinhardt.
What Proteins Are Synthesized By E Coli Cft073 In Urine
We used two-dimensional gel electrophoresis and tandem mass spectrometry to characterize the uropathogenic E. coli outer membrane subproteome 30 individual OMPs present on the bacterial surface during growth in human urine were identified. Fluorescence difference gel electrophoresis was employed to identify quantitative changes in levels of these UPEC strain CFT073 OMPs during growth in urine . Seven known receptors for iron compounds were induced in this environment: ChuA, IutA, FhuA, IroN, IreA, Iha and Hma . Induction in human urine was verified using qRT-PCR.
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Why Are Females At A Higher Risk For Utis
People with female reproductive organs are at a higher risk for UTIs because of their anatomy. The female urethra, the tube which empties urine from your bladder out of your body, is shorter than someone born with male anatomy.
The female urethra is also quite close to female reproductive organs. That means bacteria from sexual intercourse as well as products like spermicide can be in close contact with the urethra and bladder.
Females also experience menopause and pregnancy. These two biological events change the bacteria in your reproductive and digestive tracts and create conditions that make UTIs more likely.
Eau : A Sublingual Bacterial Vaccine Prevents Recurrent Uti In Women
Prophylaxis improves quality of life and reduces antibiotic and healthcare burden.
- PracticeUpdate Editorial Team
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Please Provide The Background For This Study
Recurrent urinary tract infections in women are a major health care issue. It’s not really associated with mortality it’s associated with a lot of morbidity. With more than half of women having a UTI sometime in their life, about 40% of them will be classified as having recurrent urinary tract infections. That’s more than 3 per year, and for many that can be, on average, about 6 a year. So, 3 out of 100 women every year are classified of having recurrent urinary tract infections.
The way we manage those are using things like cranberry extract, probiotics, and certainly intervaginal estrogen for perimenopausal and postmenopausal women. But the only treatment that’s really effective is antibioticseither episodic antibiotics or long-term prophylactic antibiotics that are taken for weeks and months. The antibiotics themselves are problematic. There is cost to patient and society, there is the detrimental effect of antibiotics on the patient with adverse events or effects, sometimes being quite serious and even irreversible. Antibiotics only work as long as the patient is taking the antibiotic. And then we have the rising spectra of national and international antibiotic resistance, which is becoming a huge international medical issue.
About The Fimh Vaccine
The FimH vaccine is a specific-antigen vaccine. This is a vaccine that contains a proteinin this case, the FimH bacterial adhesion proteinwhich the body recognizes as harmful. In response, the immune system will produce antibodies designed to control that specific organism.
The FimH protein works by providing E.coli the means to attach to cells on the surface of the bladder. By doing so, the bacteria can colonize and spread. Without the FimH protein, E. coli would be ill-equipped to do this.
Due to advances in DNA technology, specific-antigen vaccines have become popular vaccine models of vaccine development compared to more traditional whole-killed vaccines or inactivated vaccines.
E. coli accounts for around 90% of all UTIs, but other bacteria can cause them as well, including proteus, klebsiella, and enterococcus. The FimH vaccine would not protect against these.
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Vaccine Could Eradicate Bladder Bacteria Prevent Future Infections
In a in the Proceedings of the National Academy of Sciences, Duke researchers describe a new vaccination strategy that could reprogram the body to fight off the bacteria that cause urinary tract infections .
Although several vaccines against UTIs have been investigated in clinical trials, they have so far had limited success, says Soman Abraham, PhD, Grace Kerby Distinguished Professor of Pathology, Immunology and Molecular Genetics & Microbiology in the Duke School of Medicine and senior author of the study.
There are currently no effective UTI vaccines available for use in the U.S. in spite of the high prevalence of bladder infections, he adds. Our study describes the potential for a highly effective bladder vaccine that can not only eradicate residual bladder bacteria, but also prevent future infections.
The strategy, which the team demonstrated to be effective in mouse models, involves re-programming an inadequate immune response that was identified in 2020. Researchers observed that when mouse bladders are infected with E. coli, the immune system dispatches repair cells to heal the damaged tissue, while launching very few warrior cells to fight off the attacker. This causes bacteria to never fully clear, living on in the bladder to attack again.
A vaccine to prevent these infections will be an absolute game-changer for this patient population, says Purves.
As Antibiotic Resistance To Uti Treatments Grows Producing A Vaccine Becomes More Crucial
For most invading bacteria, the bladder is not a friendly place. But for those that have figured out how to scavenge iron from their hosts, its a fine place to grow and reproduce. For millions of women a year, this means a painful, potentially dangerous urinary tract infection.
Now, scientists have turned that iron-scavenging power against the most common UTI-causing bacteria.
For the first time, theyve prevented UTIs in mice by vaccinating them with the same molecules that the bacteria usually use to grab iron and fuel their growth. Researchers at the University of Michigan Medical School published the results in the Proceedings of the National Academy of Sciences, or PNAS.
The researchers caution that a human UTI vaccine based on the approach is still years away. But the success of vaccination with the small iron-grabbing molecules, called siderophores, paves the way for further research.
The same team previously reported success in preventing UTIs using a vaccine made of proteins from the bacteria, called uropathogenic Escherichia coli, or UPEC. Neither the protein nor the siderophore approach provided complete protection, but the two together might.
UPEC causes more than three-quarters of UTIs in otherwise healthy women, and the bacteria produce stealth siderophores that evade the host immune system and are unique to them. That makes these molecules good candidates for a vaccine without unintended consequences.
A Pressing Problem
Broadening the Research
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Game Changer Vaccine For Recurrent Utis Improves Patients Quality Of Life
Nickel JC, et al. Impact of MV140 on patient related burden of disease associated with the management of recurrent urinary tract infections . Presented at: American Urological Association meeting May 13-16, 2022 .
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A vaccine for recurrent UTIs significantly reduced UTI episodes and a need for health care resources, reducing the personal burden of disease, according to researchers.
J. Curtis Nickel,MD, FRCSC, Emeritus Professor of Urology and Canada Research Chair in Urologic Pain and Inflammation at Queens University,presented data on the polybacterial sublingual vaccine MV140 at the American Urological Association Annual Conference.
This vaccine … is going to be a game changer in patients with recurrent and chronic cystitis symptoms, he said.
In the 1-year study, patients with recurrent UTIs were randomly assigned in a 1:1:1 ratio to receive placebo for 6 months or the vaccine for 3 or 6 months. They were followed for 12 months after treatment initiation.
The researchers also observed a significant reduction in the need for health care resources among patients in the vaccine groups, as well as a significant reduction in their health care costs. The median number of antibiotic prescriptions was 4.5 for the placebo group, compared with one in both groups receiving MV140 .
Impact Of Bacterial Vaccination On Direct Healthcare Costs Associated With Ruti
Before vaccination, the mean direct annual cost per patient was 1,001.1 EUR , distributed as follows: PCP consultations , specialized care , complementary exams , and antibiotic treatments . Considering the number of UTI episodes and their associated costs , the expenditure per UTI episode before vaccination was estimated at 161.8 EUR.
Table 2.
Annual costs of consultations to healthcare system due to urinary infectious episodes
Table 3.
Annual costs of complementary tests and exams due to UTIs
Following sublingual vaccination, the mean annual cost on antibiotic treatment/patient significantly decreased from 42.7 to 16.5 EUR , albeit with different distribution depending on the antibiotic type . The use of fosfomycin involved the highest burden, followed by norfloxacin and amoxicillin/clavulanic acid. Of note, the mean number of antibiotic-resistant E. coli infections was higher in women who failed to reduce antibiotic expenditure compared to those who successfully did .
Fig. 1.
Mean costs per patient/year of the indicated antibiotic treatments before and after vaccination.
Individual costs of urine laboratory analysis, urine cultures, and ultrasounds significantly decreased by mean 0.82 , 20.1 , and 6.7 EUR per patient/year , respectively . Overall, this represents a 61.2% decrease in complementary tests .
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Vaccine For Recurrent Urinary Tract Infections
Sequoia is developing a vaccine to reduce the recurrences of Urinary Tract Infections . Sequoia has completed its first clinical study in women with and without a history of recurrent UTI. In this study, Sequoia’s investigational vaccine was highly immunogenic and well tolerated. In addition, it appears that the vaccine may indeed reduce the frequency of UTI. These preliminary results are from an uncontrolled Phase 1 clinical trial that enrolled 67 women ages 21 to 64. Of the 67 women enrolled, 30 had a 2-year documented history of recurrent UTI. Based on these positive Phase 1 results, the vaccine is proceeding to a placebo-controlled Phase 2 study.
Because Sequoias vaccine is an investigational therapy, its safety and efficacy have not been established. Sequoias vaccine requires additional studies to make any definitive conclusions about safety and efficacy. Because of the uncertainty of clinical trials, there is no guarantee that Sequoias vaccine will become commercially available. It is not approved by the FDA.
What Secreted And Outer Membrane Proteins Can Be Predicted From The Genomic Sequence Of E Coli Cft073
Using the E. coli CFT073 genome sequence, we predicted proteins that potentially localize to the bacterial cell surface by identifying signal sequences, lipoprotein motifs, -barrel structures, Hidden Markov surface prediction, integrin RGD , choline YY, transmembrane domains, and known outer membrane protein motifs. Of 5379 predicted proteins, 343 proteins were identified as potentially surface-localized .
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Expec4v: Another Vaccine Candidate
The phase 1 trial involved 188 women, 93 of whom received the vaccine and 95 of whom received a placebo. Participants were between ages 18 and 70. All had a history of recurrent UTIs.
According to the researchers, the ExPEC4V vaccine was well-tolerated and induced a significant immune response, resulting in fewer UTIs caused by E. coli.
Phase 2 results were also relatively positive. For this phase of the study, two injections were given: one on the first day of the trial and another 180 days later.
According to research published in Open Forum Infectious Diseases, women who received the ExPEC4V vaccine had a two-fold increase in the antibody response compared to those who received the placebo, who had none.
Side effects were generally mild to moderate , although they occurred at twice the rate in the vaccine group as the placebo group.
Research is ongoing.
What E Coli Cft073 Proteins Are Recognized By An Antibody Response During Experimental Uti
We applied an immunoproteomics approach to vaccine development that has been used successfully to identify vaccine targets in other pathogenic bacteria . Outer membranes were isolated from E. coli CFT073 cultured under conditions that mimic the urinary tract environment, including iron-limitation, osmotic stress, human urine, and exposure to uroepithelial cells. Outer membrane proteins were separated by 2D-PAGE and probed using pooled antisera from 20 CBA/J mice chronically infected with E. coli CFT073 . Twenty-three outer membrane antigens reacted with the antisera and were identified by mass spectrometry. These antigens also included proteins with known roles in UPEC pathogenesis, such as ChuA, IroN, IreA, Iha, IutA, Hma, and FliC. Thus, an antibody response is directed against these virulence-associated factors during UTI. Also, genes encoding ChuA, IroN, Hma, and IutA are significantly more prevalent among UPEC strains as compared to fecal-commensal E. coli isolates . Thus, conserved outer membrane antigens identified in this study could be rational candidates for a UTI vaccine designed to elicit protective immunity against UPEC infection.
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How Do Side Effects And Uses Compare To Uro
Continuing on with the discussion around side effects and the benefits of the Duke University teams vaccine, Dr. Abraham again stresses that the primary components of the vaccine are innocuous. Neither FimH nor CPG are individually toxic, and he does not believe the combination will result in a negative response.
Of course, safety studies will still be completed to ensure this expectation is accurate.
Dr. Abraham goes so far as to state his confidence that even pregnant women are unlikely to have any cause for anxiety, due to the vaccine being used directly in the bladder.
Additionally, based on current evidence, the risk of the UTI vaccine interacting with other medications, including existing vaccines like Uro-vaxom, appears to be low. In fact, there is a chance that Dr. Abrahams vaccine may boost the effectiveness of something like Uro-vaxom.
For people who are post-menopausal, have a spinal injury or interstitial cystitis , as long as the immune system is functioning, the vaccine will be able to bring T-cells to the bladder and decrease UTI risk. Dr. Abraham points out that if a persons IC has a bacterial etiology, the vaccine will of course be able to both prevent and treat UTIs.
When Will The Fimh Vaccine Be Available
Research is ongoing, and it is unknown how long it might take for the vaccine to become available to the public. Typically, it takes 10 to 15 years from the start of preclinical studies for any vaccine to gain FDA approval.
With a fast-track designation, the approval time can be shortenedsometimes significantlybut it doesn’t necessarily mean that it will or guarantee that the vaccine will ever be approved.
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Practice Healthy Hygiene Habits
Preventing UTIs starts with practicing a few good bathroom and hygiene habits.
First, its important not to hold your urine for too long. This can lead to a buildup of bacteria, resulting in infection.
Peeing after sexual intercourse can also of UTIs by preventing the spread of bacteria.
Additionally, those who are prone to UTIs should avoid using spermicide, as it has been linked to an increase in UTIs.
Finally, when using the toilet especially if you have a female urethra make sure you wipe front to back. Wiping from back to front can to the urinary tract and is associated with an increased risk of UTIs.
Benefits of healthy hygiene for UTI
Urinating frequently and after sexual intercourse can reduce the risk of UTI. Careful wiping when you use the toilet may also help decrease the risk of UTI.
Several natural supplements may decrease the risk of developing a UTI.
Here are a few supplements that have been studied and are all available in capsule form:
- D-Mannose.D-Mannose is a type of sugar that is found in cranberries. Research suggests its effective in treating UTIs and preventing recurrence.
- Cranberry extract. Like cranberry juice, cranberry extract works by preventing bacteria from adhering to the urinary tract.
- Garlic extract. shows garlic and garlic extract to have antimicrobial properties, so they it may be able to block the growth of bacteria to prevent UTIs.