What set me on the path to dedicating an entire Doc Gumshoe epistle to urinary tract infections was a statement that I ran across, asserting that these infections (which I will from this point on refer to as UTIs) are the most common infections in the US. I am not sure that statement is correct. UTIs are certainly common and frequent, but the “most common” appellation is questionable. Here are a few data points:
Here, from the World Journal of Urology, is a summary of the global impact of UTIs:
“In 2019, more than 404.6 million (95% UI 359.4-446.5) individuals had UTIs globally and nearly 236,786 people (198,433-259,034) died of UTIs, contributing to 5.2 million (4.5-5.7) DALYs. The age-standardised incidence rate increased from 4715.0 (4174.2-5220.6) per 100,000 population in 1990 to 5229.3 (4645.3-5771.2) per 100,000 population in 2019.” (World J Urol. 2022 Mar; 40(3):755-763).
DALYs, by the way, are disability-adjusted life years, which is a time-based measure that combines years of life lost due to premature mortality and years of life lost due to time lived in conditions of less than good health.
An article in Therapeutic Advances in Urology contains the following paragraph, which I find somewhat unclear:
“UTIs are the most common outpatient infections in the United States (US). With the exception of a spike in young women aged 14−24 years old, the prevalence of UTIs increases with age. The prevalence in women over 65 years of age is approximately 20%, compared with approximately 11% in the overall population. Between 50% and 60% of adult women will have at least one UTI in their life, and close to 10% of postmenopausal women indicate that they had a UTI in the previous year.” (Ther Adv Urol 2019;11,3-7)
That’s where the “most common” tag comes from, but how does one track outpatient infections? The excerpt above is from 2019, and obviously does not take into account the 100 million or so US individuals who were infected with the coronavirus. But my guess is that a colossal number of outpatient infections simply go unreported. Also, is the 20% prevalence in women over 65 an annual figure, and if so how does it sort with the 10% of postmenopausal women who indicate that they had a UTI in the previous year? My guess is that the authors of the article in Therapeutic Advances in Urology wanted to keep the most common outpatient infection in their own specialty.
This excerpt from an article about the US incidence/prevalence of UTIs is clear, but not really up-to-date, reporting only the number of patient visits for UTIs as of the five-year span between 1996 and 2001.
“UTIs are common, with an annual US incidence of 12% among women and 3% among men. UTIs are most common among sexually active women age 18-29 years. Roughly 50% of women will develop acute cystitis at least once during their lives, and about a quarter will experience recurrence. The lifetime prevalence of UTI in men is about 12%. Data from 1996-2001 reveal about 7 million patient visits per year for uncomplicated UTI. Morbidity for most UTIs is low, but because UTIs are so common, the annual cost of UTIs in the US is about $2.3 billion.” (Michigan Medicine, University of Michigan May 2021)
“Acute cystitis” is the preferred medical term for a bladder infection. Bladder infections are also (sometimes) referred to as “lower UTIs,” while kidney infections are called “upper UTIs.” More about that later.
And. according to an article in the Journal of the American Academy of Emergency Physicians, during the span between 2016 and 2018, there were 2,379,448 emergency department visits due to complicated UTIs, of which 40.1% were female, and 62.2% of these women were over 65 years of age. (JACEP; DOI; 10/1002/ emp2.12694) I find those figures somewhat puzzling. If about 40% of the ED visits due to UTIs were women, then the other 60% of those ED visits had to be men. Considering that the incidence of UTIs is about four times higher among women than among men, those figures suggest that UTIs in men, although much less frequent, are more complicated, requiring ED visits more frequently.
Causes and symptoms of UTIs
Let’s turn away from the incidence/prevalence figures to more detail about the infection itself – what causes UTIs, what are the symptoms of the infection, and, most important, how are UTIs treated?
UTIs are caused by bacteria. That’s a simple point of departure, and it distinguishes UTIs from diseases caused by other factors, which can also include viruses, fungi, and parasites. Viral infections take place when a viral particle invades a living cell in our bodies in order to reproduce, since viruses are unable to reproduce without appropriating cellular material. Fungi can live on their own, either outside our bodies or within our bodies. When they get overgrown, they can interfere with our physiologic functioning and cause illness. We can also get invaded by parasites, including some worm-like organisms and some single-celled organisms such as protozoa. They use our bodies and our cells to reproduce.
Bacteria are independent organisms. The number of bacteria that live with us in our bodies is colossal. Estimates are that we live with about 10,000 different species of bacterial organisms in our bodies, and that the total number of bacteria in our bodies is in the trillions – perhaps 30 to 40 trillion – and that they account for something in the neighborhood of 3% of our total body weight. By an enormous margin, most of these bacteria are harmless and some are actually benevolent, aiding in such matters as the digestion of our food and the maintenance of the blood-brain barriers, which works to keep harmful agents from entering our brain.
A number of common diseases are caused by bacteria, including UTIs. We should mention some of these in passing. These include sore throat and upper respiratory infections caused by Streptococcus pneumonia – i.e., strep throat. That particular bacterium can be found in the respiratory tract of vast numbers of people. As many of half of school-age children are thought to carry the strep germ.
Other common bacteria, some of which may be more common than the UTI bacterium, include Salmonella; various germs that cause sexually transmitted infections; Escherichia coli (E. coli); which cause intestinal infections, and the bacteria that cause tuberculosis and whooping cough.
The most frequent causes of UTIs are E. coli, followed by S. saprophyticus (a Staphylococcus variant). Klebsiella pneumonia and some Enterococcus variants are the frequent causes of more complicated UTIs. It happens that the specific E. coli variant most frequently associated with UTIs also increases the likelihood of recurrence within a fairly short period after the initial infection.
The symptoms of UTIs are almost self-evident. There’s that almost constant feeling of needing to empty that uncomfortable bladder, and then the burning sensation that occurs when urination takes place. Other UTI symptoms include bad-smelling, cloudy, or bloody urine.
UTIs can affect the entire urinary tract, but the pain and discomfort mostly manifest in the lower part of the tract, which includes the bladder and the urethra, which is the little tube that carries the urine out of our bodies. UTIs affecting that part of the urinary tract are called “lower UTIs.” The kidneys and the ureters (the tubes that convey urine from the kidneys to the bladder) can also be affected by UTIs, although much less frequently. Those UTIs are labeled “upper UTIs.”
What the kidneys do is filter all the blood in our bodies, removing substances that should not be in the blood such as waste products, some of which we ingest and some of which our bodies produce. The kidneys take some water from our bloodstream to carry those waste products out of the body as urine. (Needless to say, those waste products are all water-soluble – insoluble waste goes out of our bodies as feces.)
Kidney infections are much more serious, mostly requiring prompt medical attention. Kidney infections can cause lasting damage to the kidneys and can also spread to the bloodstream, resulting in a life-threatening infection known as sepsis.
Women are more susceptible to UTIs, because of their anatomy. In women, the entrance to the urethra and the distance from the anus is much shorter than in men. The entrance to the urethra is very close to the entrance to the vagina. This means that feces, and fecal bacteria, can much more easily enter the urethra. Also, the urethra in women is only about 4 centimeters long, while in men it is about 17 to 20 centimeters long. Thus, in women bacteria that enter the urethra have only a short distance to reach the bladder.
A major risk factor for UTIs is the insertion of a urinary catheter, which is often necessary for persons having surgery or being treated for certain medical conditions. Bacteria introduced by catheters are the cause of almost all hospital-acquired UTIs. The catheters themselves have been scrupulously sterilized, of course, but in the process of being inserted into the urethra, they come in contact with skin areas, which, despite precautions, may have bacteria on the surface which then get carried into the urinary tract.
Several groups of people are at higher risk for UTIs. Factors that increase the risk of UTIs include:
- Congenital malformations or dysfunctions of the urinary tract
- Prostate problems, such as benign prostate hypertrophy
- Medical conditions such as Parkinson’s disease or diabetes
- Incontinence
- Pregnancy
- Kidney stones or other kidney problems
- Anal intercourse (when the penis enters the rectum)
A specific risk factor in women that I cringe to describe is wiping from back to front after having a bowel movement. This risks bringing fecal matter directly to the opening of the urethra.
UTIs are very common in young women, starting in their teenage years. By age 24, almost a third of young women will have experienced at least one UTI requiring medical attention. The main risk factor for young women is sexual activity.
Older women are also at elevated risk for UTIs. Menopause lowers estrogen levels, which changes the bacterial populations in the reproductive and urinary tracts and thins the lining of the urethra.
After age 60, the risk of developing a UTI gradually increases in men. In men age 80 or older, the UTI rates are about the same in men and women. The UTI risk factors in older men are:
- Diabetes
- Incontinence
- Dementia
- Limited mobility
- Benign prostatic hyperplasia (BPH)
BPH is a swelling of the prostate gland which can obstruct normal urine flow. It is exceedingly common in older men. According to the NIH, about 8% of men in the 31 to 40 age range have BPH. The prevalence of BPH soars after age 50, when about 50% of men have BPH. And after age 70, the prevalence increases to 80%.
Diagnosis
When a person demonstrates the common UTI symptoms described above – that feeling of needing to empty that uncomfortable bladder, the burning sensation, and sometimes bad-smelling, cloudy, or bloody urine – the usual first step in diagnosis is collecting a urine sample in order to perform a urine culture, which involves growing out the infections bacteria in a Petri dish in the lab. This can take up to three days, during which time Pyridium (phenazopyridine hydrochloride) is often prescribed to alleviate symptoms, pending results of the urine culture. Urine cultures are more frequently done in the cases of recurrent UTIs.
Other diagnostic procedures that may be employed include chemical tests using a plastic dipstick to identify tell-tale substances in the urine. When an infection is being combated by white blood cells, a substance called leukocyte esterase is generated. An elevated level of white blood cells, known as pyuria, can be detected in almost all cases of UTI.
An enzyme called peroxidase in the urine indicates that there is blood in the urine, confirming that an infection is taking place.
In cases of recurrent UTIs, X-ray imaging may be recommended. Two types of X-rays are used in diagnosing UTIs. Intravenous pyelograms are X-rays after a dye is injected into a vein. The progress of the dye can be traced as it moves through the kidneys, ureters, and bladder. If the dye is slowed or blocked, this suggests problems with blood flow or urinary tract function.
A voiding cystourethrogram is an X-ray taken during urination, which can identify a condition in which the urine flows backward, from the bladder up the ureters and sometimes all the way back to the kidneys. This condition is called vesicoureteral reflux (VUR). It is most common in infants and young children.
In general, diagnosis of UTIs is uncomplicated, although diagnostic failings certainly do occur. Later on in this missive, I will add a case history describing such a mishap.
Treatment
For uncomplicated lower UTIs – i.e., bladder infections – the American Academy of Family Physicians (AAFP) recommends one of these fairly common oral antibiotics:
- Fosfomycin (Monourol, Cathay Drug) – 1 single dose
- Nitrofurantoin (Macrobid, Norwich Pharma) – 2 doses per day/5 days
- Trimethroprin/sulfamethoxazole) (Bactrim, McKesson) – 2 doses per day/3 days
Several other possible antibiotics have been suggested by the AAFP, including amoxicillin/clavulanate (Augmentin, US Antibiotics), cefdinir (Omnicef, Alkem Labs); and cefadroxil (Duricef, Lupin Pharma). These are taken twice a day for 5 to 7 days.
Ciprofloxacin (Cipro, Bayer) or levofloxacin (Levaquin, discontinued by Janssen in 2017 but still available) are only recommended when no other treatment options are effective. These drugs carry boxed warnings that they may cause swollen or ruptured tendons, nerve damage, anxiety, confusion, tremors, and other nervous system side effects.
A Doc Gumshoe reader, to whom I send my thanks, pointed out a couple of drugs used in UTIs that were not mentioned in the material I had at hand. One is methenamine, sold under the brand names Hiprex, Mandelamine, and Urex. These methenamine agents are all available as generics, made by about ten different manufacturers.
According to WebMD, methenamine is primarily used to prevent or reduce the chances of getting frequent UTIs, not as an immediate treatment option for UTIs.
Uromune was also mentioned by this reader. It is a vaccine against the bacteria causing UTI. Unusually for vaccines, it is administered orally rather than as an injection. It was originally developed in Spain and is available in most European countries as well as in Australia, New Zealand, and Chile. The reader pointed out that it is also available in Singapore. Development and approval in the US is in progress, but is taking longer than in other countries. It has been found to reduce total number of UTIs by about 70%, and to increase UTI-free rates from around 25% to 57%. It is an inactivated combination of the four major bacteria that cause UTIs, specifically E. coli, Klebsiella pneumoniae, Proteus vulgaris and Enterococcus faecalis. These four bacteria cause not only UTIs, but other infectious diseases. Uromune certainly appears to be a highly valuable vaccine.
I will here interject a comment and a question: it frequently takes significantly longer for new medical treatment options to achieve approval in the US. Is that because the health-care authorities in the US are legitimately more cautious, or is it because the process is more tied up in bureaucracy?
An issue that affects the treatment of all infectious diseases is the increasing prevalence of antibiotic resistance. This is a phenomenon that largely results from the way people use antibiotics, which is to say, they take the antibiotic until their symptoms recede and then they stop. What happens is that they succeed in reducing the population of the pathogens to the point that the symptoms stop, but not to the point that the pathogen population is entirely eliminated. Some of the pathogens manage to survive the onslaught of the antibiotic treatment, and it is likely that these pathogens have specific characteristics that enable them to survive. Those pathogens then multiply and form a pathogenic sub-species that possesses inherent resistance to that antibiotic.
The obvious take-away is that patients should continue taking the prescribed antibiotic for the full duration of the prescription. If the prescription specifies two tablets a day for ten days, it’s a mistake to stop after five days because the symptoms receded. The pathogens that survive at that point are the ones with resistance, and they can multiply and become the dominant species.
This issue is especially relevant in the treatment of UTIs, because in most cases treatment decisions are based on the patient’s symptoms. A study in 2020 found antibiotic-resistant E. coli in the digestive tracts of 8.8% of women tested. About a third of the women in that study had E. coli in their urine, and 77% of these E. coli were antibiotic resistant.
It has been suggested that anti-inflammatory drugs (NSAIDs) be used rather than antibiotics in treating UTIs. However, preliminary research suggests that this alternative is linked with a greater likelihood that the infection will spread to the kidneys.
Some careful conclusions
On balance, it seems that, yes indeed, UTIs are very common, and can mostly be quickly, safely, and successfully treated. The top priority is preventing the spread of the infection to the kidneys. That calls for prompt detection and intervention.
A factor in minimizing the occurrence of UTIs, which has not been mentioned up to this point, is hydration. Lots of water going in means lots of urine going out, and this helps keep the whole urinary tract active and healthy. Women, in particular, should be reminded to void after sexual activity. The urine clears the urinary tract of possible harmful invaders.
A case history
This one concerns my mother. In her late 80s, she developed a persistent UTI. She went to her regular physician, a geriatrician who was himself approaching retirement and perhaps becoming a bit inattentive. This chap, who was entertaining dreams of retiring to a life of trout fishing on the Pecos River in New Mexico, prescribed Pyridium (phenazopyridine), which does nothing more than temporarily ease the UTI symptoms. At the same time, my mother complained of backache, for which he prescribed a tricyclic antidepressant, on the theory that in elderly folks, depression was often the root cause of otherwise unexplained aches and pains.
My mother, being a very well-brought-up lass, did not communicate this to me at the time, no doubt because it would be unseemly to discuss such an intimate matter with her son. But some months later, when the regimen had failed to bring about any improvement, she brought herself to tell me about her disorder. I was more than a bit shocked. The Pyridium regimen was meant to be used for just a few days while awaiting culture results, but not continued as chronic therapy. Pyridium does not treat the infection itself, but provides some relief of symptoms. The particular antidepressant prescribed for my mother had, among its side effects, urinary incontinence. Not an advisable combo. I told her to stop both drugs at once and find another doctor.
Her new doctor confirmed my views and put her on an up-to-date antibiotic for her UTI, which by then had become chronic and perhaps more difficult to treat. But about six days after my mother started on the new drug, she developed a ferocious itch all over her body. When she telephoned me with this piece of news, I advised her to quit taking that other drug immediately. Her response, typical of a woman who had prided herself on toughness and frugality, was that it was a seven-day course, and she could just tough it out one more day.
But that same night, the itching became unbearable. She telephoned 911, and was taken to the hospital, where she was immediately given a drug to quell the itching, likely a steroid. Her new doctor was called, tut-tutted, and gave her a different antibiotic. After about a day in the hospital, she was released to a skilled nursing facility, where it was expected that she would be observed for a couple of days and then permitted to go home.
However, during her first night at the nursing facility, she felt the need to go to the toilet, slipped on the polished floor (not like her carpeted bedroom floor), fell, and broke her hip. The break did not require surgical treatment, but her movement was severely limited, and, of course, she could not go home.
She spent the last year and a half of her life in that nursing home, mostly in bed. She could take a few careful steps, but could only get to the communal spaces in a wheelchair. I visited her as often as I could; in one year I took six cross-country trips to see her. She was in tolerably good spirits, but she understood that her life was over. She died just shy of her 92nd birthday, glad to be shuffling off her mortal coil. The cause of death was heart failure.
My mother’s story illustrates a chain of errors. Her physician prescribed a totally ineffective drug for her UTI, and then cavalierly followed it up with the assumption that her backache was due to depression and not to some anatomical cause. (I should note here that antidepressants are often prescribed for fibromyalgia, a very common cause of body aches including backaches. From my perspective, this is a failure to get to the bottom of this common set of symptoms.)
How egregious was this blunder? My mother and this doctor were on pretty good terms. They travelled in the same social circle, and, knowing my mother, she may well have understated her symptoms. And she would not have been prone to question her doctor’s judgment. Her physician likely thought her ailments were no big deal, reverted to the “tried and true” nostrums of yesteryear (even though Pyridium does nothing more than mask symptoms) and forgot about it.
The downstream consequences were not trivial. If my mother had initially been treated for her UTI with any of the common, effective, and benign antibiotics that were then available, the episode would probably have resolved quickly. She would not have needed the antibiotic that led to the allergic reaction; she would not have needed to go to the hospital on an emergency basis; she would not have been released to the nursing facility; she would probably not have fallen and broken her hip.
I cannot say for sure that this chain of events lead to her untimely death. What seems clear is that the casual treatment she initially received had a severe impact on her quality of life in her last couple of years on Planet Earth. And it’s entirely possible that if the initial treatment for her UTI had been correct, she might have had several more years of life.
* * * * * * *
There continues to be lots of stuff happening that will furnish grist for Doc Gumshoe’s mill. The NYTimes had a front and multi-page piece on the shocking concealment of serious issues by a leading pharmaceutical company concerning one of its lead drugs. At the same time, another big pharma has come up with the first totally new antibiotic in years. As you may know, pharmaceutical companies are not eager to lavish billions (yes, billions!) on bringing new antibiotics, for a variety of reasons which I will go into. And, there may be signs of hope in treatment options for Alzheimer’s. I’ll get to work on those in the next couple of weeks.
Best to all, and many, many thanks for the comments! Michael Jorrin (aka Doc Gumshoe)
[ed note: Michael Jorrin, who I dubbed “Doc Gumshoe” many years ago, is a longtime medical writer (not a doctor) and shares his commentary with Gumshoe readers once or twice a month. He does not generally write about the investment prospects of topics he covers, but has agreed to our trading restrictions. Past Doc Gumshoe columns are available here.]
