Combination of pills could help patients avoid resistant UTIs, study shows

Older people with recurring bouts of urinary tract infection (UTI) may benefit from a combination of antibiotics to treat superbugs, rather than just a single drug, a study has shown.

Researchers at Newcastle University have observed for the first time how bacteria resist certain antibiotics by shedding their cell wall – a vital target of many of the most common drugs.

But by giving a combination of antibiotics that target different parts of the cell researchers believe that drug resistance could be avoided.

Antimicrobial resistance is an increasing global threat, with a recent report from the United Nations warning that if left unchecked it could kill 10 million people by 2050.

Drug-resistant UTIs are a particular problem, with a Public Health England analysis of more than a million samples showing that a third were resistant to a previously commonly used antibiotic, trimethoprin.

The research, published in the journal Nature Communications, looked at 30 elderly patients who donated samples of urine every two weeks over a six-month period. All the patients suffered recurrent UTIs, a common problem among older people.

The research captured on film for the first time bacteria isolated from a patient with UTI re-forming a cell wall after the antibiotic had gone – taking just five hours.

The team was also able to show by a direct microscopy in transparent zebrafish model, that this switching is possible in a living organism and not only in artificial conditions in the lab.

The study found that in a healthy patient the bacteria without the cell wall is destroyed by their hosts’ immune system. But in patients whose immune systems are compromised the bacteria can reform their cell wall and the patient has another infection.

“This may well be one of the main reasons why we see people with recurring UTIs,” said Dr Katarzyna Mickiewicz, lead author of the study and a researcher at Newcastle University.

She said doctors should consider giving patients with recurrent infections a combination of antibiotics - one that targets the bacteria’s membrane and another that targets the wall.

“Membrane-targeting antibiotics are good against bacteria but highly toxic to humans. They are generally last-resort antibiotics but in combination with a cell-wall targeting antibiotic they could work well in patients,” she said.

Patients are generally given just one type of antibiotic at a time, said Dr Mickiewicz.

“From what I have seen in the study patients were getting just one lot of antibiotics at a time and were then given another one, rather than being given two at once. This happens in the United States but is not a common practice here,” she said.

She added that there are many ways that bacteria develop drug resistance so this pill combination would only work against bacteria that target the cell wall.

She said that next steps were for researchers to look at other infections such as sepsis and lung infections.

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