Chronic LUTS in patients with negative midstream urine (MSU) cultures can be successfully treated with prolonged antibiotic therapy, according to a UK study.
Researchers from the Lower Urinary Tract Symptoms Clinic at London's Whittington Hospital, which specialises in treating chronic UTI, analysed data from 624 women with chronic LUTS and pyuria who were treated over a 10-year period.
Pyuria, detected by microscopy of an MSU specimen, is considered the most sensitive surrogate marker of UTI. The researchers argue that negative dipstick testing and negative MSU cultures cannot reliably exclude UTI, and hypothesised that chronic LUTS may result from urinary infection falling below the routine culture threshold.
Patients received first-line, narrow-spectrum oral antibiotics typically used for UTI, such as nitrofurantoin, trimethoprim or cefalexin. The urinary antiseptic agent methenamine hippurate (Hiprex) was given as an adjunct, and some patients required combination antibiotic therapy. All patients who completed treatment were also given back-up antibiotics to take at the first sign of symptom recurrence.
Prior to presentation, the mean duration of the women's symptoms was 6.5 years. Only 16% of MSU cultures submitted were positive.
Treatment was associated with a reduction in total LUTS (p=0.0001), 24-hour frequency (p=0.0001), urinary urgency (p=0.0001), lower urinary tract pain (p=0.0001), voiding symptoms (p=0.002) and pyuria (p=0.0001). Overall, 64% of women reported that their symptoms were very much better, and a further 20% reported that they were much better.
Long-term therapy was required, with patients being treated for an average of 383 days.
No increase in bacterial resistance
A total of 475 adverse events was recorded during 273,762 treatment days, all but one of which were classified as mild to moderate. The median number of antibiotics to which the MSU culture isolates were resistant remained at one over all visits. The researchers suggest that the use of methenamine, which has a non-selective bactericidal effect in the urinary tract, may generate less bacterial resistance than using conventional antibiotics alone.
The researchers call for their treatment protocol to be tested against the approach recommended by current guidelines.
'Oral antibiotics are an effective treatment for chronic urinary tract infections and support the idea that the symptoms are caused by bacterial infections,' said lead author Dr Sheela Swamy. 'These results provide preliminary data to inform further randomised control trials.'