In the Journals

Antibiotic prophylaxis for recurring UTIs effective; resistance a concern

Continuous antibiotic prophylaxis was effective in preventing recurrent urinary tract infections among clean intermittent self-catherization users who are at risk for the infection, according to study findings recently published in The Lancet Infectious Diseases. However, researchers observed increasing levels of antibiotic resistance with prophylaxis use, which they said “limits the appeal” of the prevention strategy.

“The 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 colonize urine and contribute to the fecal microbiome are a public health concern,” Holly Fisher, PhD, of the Institute of Health and Society at Newcastle University, and colleagues wrote. “The severity of individual patient distress from repeated [urinary tract infections (UTIs)] and local threats from antimicrobial resistance should simultaneously be considered when appraising and implementing this evidence of benefit of treatment.”

Patients with certain conditions, such as multiple sclerosis and urinary sphincter relaxation failure, use clean intermittent self-catheterization (CISC) to help empty their bladders. In England, there are about 74 CISC users per 100,000 people, according to the researchers.

Previous evidence suggests that approximately 25% of CISC users develop recurrent symptomatic UTIs. To address this issue, Fisher and colleagues conducted a randomized, open-label trial to assess the benefits and harms of a continuous, low-dose antibiotic prophylaxis regimen in adult CISC users in the United Kingdom.

More than 400 participants were enrolled in the study between November 2013 and January 2016. Half of them were randomly assigned to receive once-daily antibiotic prophylaxis, which included nitrofurantoin (50 mg), trimethoprim (100 mg) or cefalexin (250 mg). Physicians prescribed treatment based on individual patient information. The primary outcome was the difference in self-reported symptomatic UTIs treated with antibiotics between the intervention and control groups over 12 months.

The incidence of symptomatic antibiotic-treated UTIs was 1.3 cases per person-year (95% CI, 1.1-1.6) in the intervention group and 2.6 cases per person-year (95% CI, 2.3-2.9) in the control group, yielding a 48% reduction in UTI frequency with antibiotic prophylaxis, according to the researchers.

Antibiotic prophylaxis was generally well-tolerated. Twenty-two mild adverse events related to prophylaxis use were reported. Most adverse events included gastrointestinal disturbance (n = 6), skin rash (n = 6) and Candida infection (n = 4).

Compared with the control group, the intervention group had higher levels of resistance to drugs used for prophylaxis as well as common UTI treatments, including nitrofurantoin (24% vs. 9%), trimethoprim (67% vs. 33%) and co-trimoxazole (53% vs. 24%).

An economic evaluation indicated that antibiotic prophylaxis was potentially cost-effective, according to the researchers. In a related editorial, however, Florian M.E. Wagenlehner, MD, PhD, and Adrian Pilatz, MD, of the Clinic for Urology, Pediatric Urology and Andrology at Justus Liebig University Giessen in Giessen, Germany, warned that it is difficult to calculate the financial burden of antibiotic resistance caused by long-term drug use.

Wagenlehner and Pilatz also noted that the study design may have restricted the clinical implications of the results. For example, because the study was not placebo controlled, patients in the control group who knew they were not receiving antibiotics may have overestimated their UTI symptoms. The authors also said the study would have been better designed had UTIs been confirmed at a clinical visit.

“In summary, this study gathers important evidence in a specific patient population,” they wrote. “However, the slight advantages to antibiotic prophylaxis that were found by Fisher and colleagues might not be transferable to other health care systems.” – by Stephanie Viguers

Disclosures: Fischer reports receiving grants from the National Institute for Health Research Health Technology Assessment Program. Pilatz reports no relevant financial disclosures. Wagenlehner reports serving as a scientific advisor for Achaogen, AstraZeneca, Bionorcia, Enteris BioPharma, Helperby Therapeutics, Janssen, LEO Pharma, MERLION, Merck, OM Pharma, Pfizer, Rosen Pharma, Shionogi and VenatoRx Pharmaceuticals. Please see the study for all other authors’ relevant financial disclosures.

Continuous antibiotic prophylaxis was effective in preventing recurrent urinary tract infections among clean intermittent self-catherization users who are at risk for the infection, according to study findings recently published in The Lancet Infectious Diseases. However, researchers observed increasing levels of antibiotic resistance with prophylaxis use, which they said “limits the appeal” of the prevention strategy.

“The 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 colonize urine and contribute to the fecal microbiome are a public health concern,” Holly Fisher, PhD, of the Institute of Health and Society at Newcastle University, and colleagues wrote. “The severity of individual patient distress from repeated [urinary tract infections (UTIs)] and local threats from antimicrobial resistance should simultaneously be considered when appraising and implementing this evidence of benefit of treatment.”

Patients with certain conditions, such as multiple sclerosis and urinary sphincter relaxation failure, use clean intermittent self-catheterization (CISC) to help empty their bladders. In England, there are about 74 CISC users per 100,000 people, according to the researchers.

Previous evidence suggests that approximately 25% of CISC users develop recurrent symptomatic UTIs. To address this issue, Fisher and colleagues conducted a randomized, open-label trial to assess the benefits and harms of a continuous, low-dose antibiotic prophylaxis regimen in adult CISC users in the United Kingdom.

More than 400 participants were enrolled in the study between November 2013 and January 2016. Half of them were randomly assigned to receive once-daily antibiotic prophylaxis, which included nitrofurantoin (50 mg), trimethoprim (100 mg) or cefalexin (250 mg). Physicians prescribed treatment based on individual patient information. The primary outcome was the difference in self-reported symptomatic UTIs treated with antibiotics between the intervention and control groups over 12 months.

The incidence of symptomatic antibiotic-treated UTIs was 1.3 cases per person-year (95% CI, 1.1-1.6) in the intervention group and 2.6 cases per person-year (95% CI, 2.3-2.9) in the control group, yielding a 48% reduction in UTI frequency with antibiotic prophylaxis, according to the researchers.

Antibiotic prophylaxis was generally well-tolerated. Twenty-two mild adverse events related to prophylaxis use were reported. Most adverse events included gastrointestinal disturbance (n = 6), skin rash (n = 6) and Candida infection (n = 4).

Compared with the control group, the intervention group had higher levels of resistance to drugs used for prophylaxis as well as common UTI treatments, including nitrofurantoin (24% vs. 9%), trimethoprim (67% vs. 33%) and co-trimoxazole (53% vs. 24%).

An economic evaluation indicated that antibiotic prophylaxis was potentially cost-effective, according to the researchers. In a related editorial, however, Florian M.E. Wagenlehner, MD, PhD, and Adrian Pilatz, MD, of the Clinic for Urology, Pediatric Urology and Andrology at Justus Liebig University Giessen in Giessen, Germany, warned that it is difficult to calculate the financial burden of antibiotic resistance caused by long-term drug use.

Wagenlehner and Pilatz also noted that the study design may have restricted the clinical implications of the results. For example, because the study was not placebo controlled, patients in the control group who knew they were not receiving antibiotics may have overestimated their UTI symptoms. The authors also said the study would have been better designed had UTIs been confirmed at a clinical visit.

“In summary, this study gathers important evidence in a specific patient population,” they wrote. “However, the slight advantages to antibiotic prophylaxis that were found by Fisher and colleagues might not be transferable to other health care systems.” – by Stephanie Viguers

Disclosures: Fischer reports receiving grants from the National Institute for Health Research Health Technology Assessment Program. Pilatz reports no relevant financial disclosures. Wagenlehner reports serving as a scientific advisor for Achaogen, AstraZeneca, Bionorcia, Enteris BioPharma, Helperby Therapeutics, Janssen, LEO Pharma, MERLION, Merck, OM Pharma, Pfizer, Rosen Pharma, Shionogi and VenatoRx Pharmaceuticals. Please see the study for all other authors’ relevant financial disclosures.