The antibiotics used as prophylaxis in this study were 50mg nitrofurantoin, 100mg trimethoprim, or 250mg cephalexin (all once-daily). The control group received no prophylaxis (there was no placebo).
A total of 404 participants were randomised and 361 (89%) included in the primary analysis; the remainder (22 participants in the prophylaxis group and 21 participants in the control group) were excluded as they were missing follow-up data before 6 months.
Despite the positive primary findings, resistance against the antibiotics used for UTI treatment was more frequent in urinary isolates from the prophylaxis group than in those from the control group (nitrofurantoin: 24% prophylaxis vs 9% control; p=0.038; trimethoprim: 67% vs 33%; p=0.0003; co-trimoxazole: 53% vs 24%; p=0.002).
An economic evaluation suggested that the incremental cost of the antibiotic prophylaxis strategy was £99 per UTI avoided, and that there was a 60% chance it would be cost-effective should society be willing to pay £200 to avoid a UTI. The true expense of antibiotic resistance is however difficult to calculate.
The researchers note that long-term implications of this intervention are uncertain, but increased pathogen resistance might make it more difficult to treat established infections in individuals, and increased resistance of bacteria that colonise urine and contribute to the faecal microbiome are a public health concern. The severity of individual patient distress from repeated UTIs and local threats from antimicrobial resistance should simultaneously be considered when appraising and implementing this evidence of benefit of treatment.
According to the authors of a related comment, this study gathers important evidence in a specific patient population. However, the observed slight absolute advantages to antibiotic prophylaxis might not be transferable to other health-care systems.