Thoughts on Chronic Urinary Tract Infections

Today I was reading a CME article on chronic urinary tract infections by Brubaker et al, describing the new AUGS guidelines for treatment of this condition. It was an excellent article, going through epidemiology of the condition, appropriate antibiotics, etc.

What I found interesting is the very mild treatment of the concept of urinary biofilms and their role in chronic urinary tract infection. This is an area that is well studied in other areas of chronic infection. For example, endocarditis, or chronic infection of a heart valve, is well known to be a biofilm process. Similarly, infection of a permanent orthopedic implant like an artificial hip, is also known to be a biofilm process. But strangely, the idea that a chronic urinary tract infection is a biofilm process is usually looked at as an 'out there' idea, and some even think its quackery practiced by so-called urinary infection 'specialists'.

Well call me a quack I guess, because I think that biofilms are definitely part of chronic urinary tract infection. And why shouldn't they be? If a urinary tract infection were only infection in the urine itself without any reservoir in the bladder tissue itself, we would expect 100% cure rate with treatment with appropriate antibiotics. But we don't see that. In fact, according to this article, up to 40% of women will have recurrence of their urinary tract infection in a short period of time after treatment.

The simplistic explanation to this is that the woman is being reinfected by the same source as where she got the first one. But I think this is probably only what happens sometimes. Biofilms in the bladder wall are really a better answer.

So what is a biofilm? Its basically a colony of bacteria that are growing on a surface. In many cases, the bacteria has laid down a layer of mucous and other tissue that allows a film to accumulate on the bladder wall. We have all seen this in our showers if we are not good at keeping it clean, where fungal and bacterial growth forms a sticky film that is hard to get off. Not even the 'scrubbing bubbles' gets it done every time. Same thing can happen in the body, and I believe it is happening in urinary tract infection at times.

The article makes a brief mention of this:

"Uropathogenic E. coli have special features that facilitate urothelial attachment, allowing the microbe to take up residence within the bladder. Uropathogenic E. coli can form intracellular bacterial communities that act like a biofilm, allowing bacteria to persist in quiescent intracellular reservoirs, acting as a source of recurrent infection."

So if bugs are forming biofilms, how do we treat and diagnose them?

This isn't entirely established. There are a lot of expert protocols, some of which I follow. But there are not really well established evidence that really proves what the right thing to do is.

What I do is a two pronged approach:

1) First, if a patient seems to have chronic urinary tract symptoms but has a negative urine culture, I use DNA based culture to see if there are bacteria in the urine that are not being picked up on the culture. Presumably, if there is a negative urine culture but there is lots of bacterial pathogen DNA in the urine, this is because the bacteria are not in solution in the urine but are rather living in a biofilm on the bladder wall.

2) second, if she has proven biofilm, or just keeps getting reinfected despite adequate treatment, I tend to use instilled antibiotics into the bladder. We also use a solution of 'bladder-buster' chemicals that help to break up the biofilm and allow the antibiotics to penetrate (1% EDTA most commonly).

This is also briefly mentioned in the article

"Gentamicin has been the antibiotic most studied for bladder irrigation.114–116 There have been no randomized controlled trials performed to date, and all reports have been case series in individuals with complicated UTIs. Reports have included findings from in vitro, animal, and human studies. Bladder instillation regimens have included gentamicin solutions with concentrations ranging from 40–80 mg gentamicin with 50 mL normal saline; instillation volumes of 30 to 60 mL with at least a 1-hour or overnight dwell have been recommended. No elevated serum gentamicin levels were recorded, and all studies reported a meaningful reduction in UTIs while instillations were performed. Specialists may use this therapy in select patients, despite the lack of evidence from robust comparison studies. Limited current evidence supports the safety of gentamicin bladder instillations."

The final issue worth discussion, which isn't discussed at all in this article, is whether or not some cases of interstitial cystitis are actually cases of chronic biofilm urinary tract infection that have never been diagnosed. I believe personally that this is true. I have seen throughout my career that a population of women with "IC" seem to have less symptoms when they are on oral antibiotics, even though they have negative urine cultures. In recent years, whenever I have seen such a patient I have gotten DNA based cultures, and lo and behold they are often positive. This leads me to believe that these people do in fact have chronic urinary tract infection, and that their "IC" symptoms may actually be best treated with longer courses of intravesical and oral antibiotics.

This particular thought process is not well supported in the literature, but also it is not disproven either. Basically it is unstudied. It is worth studying and publishing on though, and hopefully we will see data on it soon.

Thank you for reading.

Nicholas Fogelson, MD

Founder, Northwest Endometriosis and Pelvic Surgery