Back to the future for UTI antibiotics

Many multidrug resistant bacteria remain susceptible to two antibiotics discovered back in the 1950s and 60s

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It appears everything old is new again in the world of antibiotics for treating uncomplicated urinary tract infections in women.

Antibiotic resistance rates are high – and on the rise – in bacteria that cause cystitis in Australia. Resistance to Escherichia coli has reached around 16-43% for common antibiotics.

At the moment, a number of women with uncomplicated, antibiotic-resistant UTIs are being admitted to hospital for treatment because most of the newer antibiotics are intravenous.

However, there are two “forgotten” antibiotics, nitrofurantoin and fosfomycin, that are still very potent against many resistant strains of bacteria that cause cystitis – and can be taken orally.

Monash University researchers recommended the use of these two antibiotics for treating uncomplicated UTIs in women in a paper published in Australian Prescriber this month.

These old antibiotics were effective as they built up high concentrations in the urinary tract, infectious disease physician Professor Anton Peleg and his co-authors wrote. 

There were also well-tolerated and had a minimal impact on gastrointestinal flora.

Nitrofurantoin was discovered in 1953 and had been available in Australia since the 1970s. Its mechanism is not fully understood but the drug is thought to work by inhibiting protein synthesis and interfering with bacterial ribosomal proteins.

It’s active against the common causes of cystitis, and resistance to it is uncommon (around 1-2% for E. coli in Australia). 

Nitrofurantoin’s cure rates match those of other antibiotics, ranging from 79-92%.

The drug can be used during pregnancy, but it is not recommended beyond 38 weeks’ gestation due to the risk of haemolytic anaemia in neonates.

“It is also best to avoid during the first month of breastfeeding,” the authors said.

The drug is taken orally as a 50-100 mg capsule four times daily.

“There is a long-acting formulation available overseas, but not in Australia,” the authors wrote.

Fosfomycin has lower cure rates than nitrofurantoin (58% versus 70% in one recent randomised trial), but it has the advantage of being prescribed as a single 3g dose.

“This single-dose regimen is attractive due to better adherence,” the authors wrote.

While nitrofurantoin can be prescribed for children over one month of age, fosfomycin is only TGA-approved for treating uncomplicated lower UTIs in females aged over 12. Nitrofurantoin was named as a preferred drug to treat UTIs in international consensus guidelines in 2010 due to its lower rates of “collateral damage” on gastrointestinal flora.

But fosfomycin is usually reserved in Australia for treating patients for whom first-line drugs are not an option. 

“Part of the rationale behind this is to minimise the emergence of resistance and prolong the usefulness of fosfomycin for patients without alternative options,” the authors said.

“As resistance to other drugs inevitably rises and local experience increases, fosfomycin may become a first-line option in the future.”