BURNING question: Why can’t doctors help end the misery of urine infections?
BY now I can sense an infection coming on, even before the searing pain strikes. It has caused me to miss birthday celebrations and cancel date nights with my husband, but worst of all is the crushing sense of disappointment and frustration when another course of antibiotics fails, together with the anxiety that I may never shake this thing off.
For the past three years, I have suffered from persistent cystitis, a urinary tract infection (UTI) — I have had around 13 episodes in that time, but towards the middle of 2018, they all began to merge into one constant attack.
Long-term, low- dose antibiotics have given me some respite — but not cured it.
However, there is growing suspicion among specialists that what might be needed to treat chronic or recurrent UTIs like mine is not low or no doses of antibiotics, but very strong ones, to attack resistant ‘biofilms’ that may have taken hold in the bladder.
UTIs are the most common bacterial infection in the UK, accounting for between 1 and 3 per cent of GP visits. More than half of women will experience at least one, but men and children are also affected.
The infections are often dismissed as ‘bladder colds’ that can be shaken off by drinking plenty of water, but failing to seek medical attention is risky. ‘Ignoring symptoms runs the risk of it evolving into a chronic UTI,’ says Dr Catriona Anderson, a GP in newcastle-under-Lyme, who specialises in their treatment. This is when the bugs causing the infection are never completely cleared and so symptoms come back.
The Chronic Urinary Tract Infection Campaign (CUTIC) estimates that up to 1.6 million women in the UK suffer from chronic or recurrent UTIs: ‘It is life-limiting,’ says Susan Yates, director of CUTIC. ‘You often are unable to work even on a part-time basis and many find it a difficult, embarrassing condition to discuss with an employer. You can’t be intimate with your partner, because if you are, you’re worried, “will it trigger another flare?” ’
The condition, which causes dreadful pain passing water and constant discomfort, starts when ‘bad’ bacteria multiply in the bladder, attacking its lining and that of the urethra, the tube that takes urine out of the body.
Current guidance from the national Institute for Health and Care Excellence (nICE) is to prescribe a short course of antibiotics if these symptoms don’t resolve themselves within 48 hours.
Antibiotics work in around 70 per cent of patients — although a sub-group of patients, 2.4 per cent, will go on to develop frequent, even constant, infections.
NICEguidelines suggest daily low- dose antibiotics in cases of recurrent UTIs, defined as suffering three or more infections per year. However, there are no guidelines for chronic UTIs, where people have constant symptoms.
worse, some GPs will only prescribe antibiotics if a urine culture or dipstick test confirms an infection, but recent studies have suggested these may miss half to two-thirds of infections.
In 2016, I developed a recurrent UTI. Each time I went to my GP, a test would confirm E. coli in my urine, and I’d be prescribed antibiotics — but as soon as I stopped taking them, it would return.
My GP referred me to a urologist who suggested a constant low dose of the antibiotic nitrofurantoin, daily for six months.
This is the standard approach — for many years, the assumption has been that recurrent UTIs were the result of re-infection with bacteria from outside the bladder. Hormonal changes such as a fall in oestrogen around the menopause can also make tissues in the urethra and vulva more fragile, increasing the infection risk.
However, a growing number of experts now believe the problem stems from bacteria setting up
colonies within the cells lining the bladder. These nests of bugs form a ‘biofilm’ that’s largely impervious to antibiotics: standard doses don’t penetrate deep enough into the tissues to kill them.
The infected bladder cells send distress signals to the immune system, but this doesn’t help: ‘white blood cells turn up to fight the infection, but they can’t see that there’s anything wrong as the bacteria have figured out ways to “hide” from them and from the drugs,’ explains James MaloneLee, a consultant physician and a professor of medicine at University College London, who runs a private clinic for chronic UTI patients. ‘This infection can sit with you for years and years.’
The existence of biofilms was first demonstrated in mice around 16 years ago. Meanwhile, a review by the respected Cochrane group in 2004, found that although 79 per cent of women remained symptom-free while taking prophylactic antibiotics, this dropped to 18 per cent as soon as they stopped: suggesting that the drugs aren’t killing the bacteria.
‘This [biofilm hypothesis] seems to fit with what we observe in our patients, although it has been difficult to prove it in humans definitively,’ says Ased Ali, a consultant urologist and UTI researcher at Mid Yorks Hospitals nHS Trust.
If a biofilm is responsible for my infection, then the low-dose antibiotics I’ve been taking as prophylaxis may be merely suppressing it, not ridding me of it. This fits with my experience: when my GP asked me to stop the drugs after six months to see if I was better, I had full-blown cystitis within a week. I have been back on them ever since. So I go to see Professor Malone-Lee.
He puts a drop of my urine sample onto a microscope slide, directing my attention towards round, smudgy white blood cells — indicative of my body trying to fight an infection.
He also points out some long, flat cells, that have folded over on themselves: these are epithelial cells which usually line the bladder, but are shed in higher numbers during a UTI, as the body tries to rid itself of infected cells.
A urine dipstick test reveals the presence of nitrite, a chemical produced by certain bacteria which are frequently associated with UTIs, and further evidence of white blood cell activity. Even though I’m taking prophylactic antibiotics and have no symptoms, these results — combined with my clinical history — suggest my infection is still there, he concludes.
It’s depressing news. But Professor Malone-Lee has a plan.
For patients like me, his solution is a prolonged course of a highdose antibiotic: usually cefalexin, but sometimes nitrofurantoin or trimethoprim. He combines this with a drug called methenamine hippurate ( or Hiprex) which breaks down in urine, releasing ammonia and formaldehyde, making it an antiseptic.
‘There is a huge variance, but on average it takes us a year to get to the stage where we can start trying to take you off the antibiotics,’ he says. ‘ But then again the average amount of time that people have been suffering by the time they get to us is 6½ years.’ My case is comparatively mild, so I might respond to Hiprex alone.
The theory is that these higher dose antibiotics are better able to penetrate the bladder lining and kill the bugs, and if they try to escape into the bladder, they will also be targeted by the Hiprex.
Some bacteria will respond to the antibiotics by becoming dormant, but the cells they are hiding in will gradually be sloughed off, and replaced with new ones: it takes around nine months for the bladder wall to renew itself.
Dr Anderson and Mr Ali advocate a similar approach with their patients — although they also send the urine samples to be cultured, using the results to decide which antibiotic to prescribe.
on top of this and Hiprex, they advise patients with an E.coli infection to take a supplement called D-Mannose, a form of sugar that is undergoing trials to treat UTIs. It is thought to mimic a substance the bacteria cling to on the surface of bladder cells while trying to infect them — the theory is that it helps to mop up the bacteria by acting as a decoy.
DrAnDErSon also advises avoiding caffeine, sugar and alcohol — especially white and sparkling wine — all of which seem to trigger symptoms in her patients, and taking care around sexual activity (passing urine before and after sex, and washing beforehand).
It could be up to a year before I know if this treatment has worked, but I am cautiously optimistic.
Even for many doctors specialising in urology or gynaecology, the idea of biofilm infections is relatively new. ‘ The criteria we currently use for making a diagnosis [of UTIs] are quite antiquated and don’t have very robust evidence to support them — and that is partly where the problem is,’ says Swati Jha, a spokesperson for the royal College of obstetricians and Gynaecologists.
‘There is a cohort of women who have UTI-like symptoms, but who don’t grow the bugs. That’s where the biofilm hypothesis has a lot of credibility, I think.’
But she stresses that more research is needed.
Professor Helen StokesLampard, chair of the royal College of GPs, concurs: ‘Additional research into extending antibiotic prescribing for UTIs is very important — it’s vital that this and other research is taken into account as clinical guidelines are updated.’